diagnosis and treatment of malignant lymphoma

8/21/2019 Diagnosis and Treatment of Malignant Lymphoma

1/5

Jpn J Clin OncoI1998;28 4 245-249

iagnosis and Treatment Malignant Lymphoma the ParotidlandNaoki Hirokawa1 Masato Hareyama1 Hidenari Akiba1 Masaaki Satoh2, Atsushi Oouchi1Mitsuharu Tamakawa1, Koh-ichi Sakata1, Hisayasu Nagakura1, Kazumitsu Koito1, Kazuo Morita1,Yasuaki Harabuchi3 Akikatsu Kataura3 and Yuji Hinoda4Departments of 1Radiology 2Clinical Pathology 30tolaryngology and 4First Internal Medicine Sapporo MedicalUniversity School of Medicine Sapporo Japan

Background: To correlate the imaging and pathological features and to discuss therapeuticmodalities andthe prognosis of malignant lymphoma originating in the parotid gland which isrelatively rare.Methods: The subjects were five patients with malignant lymphoma originating in the parotidgland. Three andtwopatients were stage Iandstage II respectively. CTexamination wasappliedto all whereas onlyonecase wasexamined by MRI. Allweretreated with radiotherapy followingsurgery or chemotherapy. Three patients underwent combination chemotherapy such as withMACOP-P or VEPA following surgery.Results: Although malignant lymphoma originating inthe parotid gland is histologically describedas low-grade non-Hodgkin s lymphoma twoandoneofthecases were classified as intermediateandhigh grade inthe present series respectively. These three exhibited a tendency for infiltrationintotheadjacent tissue andtumor inhomogeneity inthe imaging findings suggesting a correlationwith histologically intermediate or high-grade non-Hodgkin s lymphoma. It was successfullycontrolled by radiotherapy with dosages ranging from 40 to 44 Gy. Thepatients werefollowed for 8years. No relapse wasfound inthe three patients with stage I However bothstage IIpatientshad relapses andwere subjected to additional radiotherapy combined withchemotherapy. Sincethen no tumor relapse hasbeen noted ateitherthisor othersites.Conclusions: Malignant lymphoma including intermediate orhighgrade originating intheparotidgland indicated satisfactory prognosis following radiotherapy and chemotherapy.Key words: malignant lymphoma - parotid tumor - radiotherapy - chemotherapy - CT - MR

INTRODUCTIONIt has been reported that primary tumors of the parotidgland showno characteristic features in diagnostic imaging, reflecting noneof their histological findings 1). Therefore, it is difficult todifferentiate benign conditions from malignant tumors and mostpatients are subjected to surgical procedures before a definitivediagnosis has been made. The head and neck region is the mostcommon site where malignant lymphomas occur, but malignantlymphoma of the parotid gland is relatively rare 2). As statedbefore, the imaging features are non-contributory to a diagnosis

Received August 27, 1997; accepted December 17, 1997For reprints and all correspondence, Naoki Hirokawa, Department ofRadiology, Sapporo Medical University, School of Medicine, South-l,West-16, Chuo-ku, Sapporo 060, JapanAbbreviations: MACOP-P, cyclophosphamide, doxorubicin, vincristine,methotrexate, pepleomycin, predonisolone; VEPA, vincristine,cyclophosphamide, doxorubicin, prednisolone

and the majority of patients are surgically treated. However,radiotherapy and chemotherapy are also effective, often with afavorable prognosis, so it is desirable to differentiate malignantlymphoma of the parotid gland from other tumors prior to surgery.We recently encountered five cases of malignant lymphoma ofthe parotid gland. The purpose of this paper is to present the CTand MRI fmdings, therapeutic modalities and the prognosis ofmalignant lymphoma of the parotid gland.MATERIALS AND METHODSThe subjects were five patients with malignant l ymphomaoriginating in the parotid gland. They had been treated at theDepartment of Radiology, Sapporo Medical University, betweenSeptember 1985 and January 1995. The patients one male andfour females) ra nged from 44 to 74 years of age mean 55.4years). No patients suffered complication of facial nerve palsy orSjogren s syndrome. Patients were staged according to the AnnArbor criteria. All specimens were stained with hematoxylineosin and monoclonal antibodies CD20, CD45RO) and classi-


2/5

6 Malignant lymphoma the parotid gland

fied according to the working formulation WF). The characteristics seen at CT and MRI imaging of the parotid gland, such astumor size, tumor margins, signal intensity, tumor homogeneityand tumor infiltration into adjacent tissues, correlated withmalignant lymphoma. The CT examination was applied to all,whereas only one case was examined by MRI. As a therapeuticpolicy, all were first subjected to surgical procedure, whichincluded total parotidectomy for one, superficial parotidectomyfor two and biopsy for two cases. Of the two patients whounderwent superficial parotidectomy, the procedure was combined with cervical lymph node dissection in one. Three and twopatients were stage I and stage II, respectively. Bilateral cervicallymph node involvement was noted in both stage II patients. Inthree cases the surgical procedure was followed by chemotherapy. All were treated with radiotherapy following surgery or

Table 1. Patients characteristics

chemotherapy. The radiation dosage applied to the tumor rangedfrom 40 to 44 Gy.

RESULTSP THOLOGI L FINDINGSAccording to the WF classification, two patients had diffuse largecells as intermediate grade, one had diffuse small cleavedimmunoblastic type cells as high grade and one had follicularmixed cell type as low grade. The remaining patient had MALTlymphoma Table 1).When classified by surface markers, all fivecases belonged to the B-cell type. When the primary site wasclassified by the location, the tumor was situated in the superficiallobe in three cases, deep lobe in one case and both in one case.

Case

23

45

Age Sex Histopathological Cell type Stage Lobeclassification

47 Male F.Mixed B II L-superficial61 Female D. Large B II L-deep44 Female D. Small cleaved, B ~ s u p e r f i c i l

immunoblastic51 Female MALToma B L-superficial74 Female D. Large B R-both

R, right; L, left.

Tabl e 2. CT or MR i magi ng of the par ot id t umor

Case

2

3

4

5

Size mm)22 x 8 x 30

55 x 38 x 83

34 x 24 x 58

18 x 12 x 28

41 x 36 x 55

HomogeneityHomogeneous

Inhomogeneous

Inhomogeneous

Homogeneous

Inhomogeneous

MarginWell

III

III

III

III

Edema

+

Infiltration

v

v

Cystic change

GrowthModerate

Rapid

Rapid

Moderate

Rapid

Well, well defined; ill ill defined; s, subcutaneous tissue; m, muscle; v, vessel.


3/5

Figure 1.MR image ofcase 3.The tumor inthe superficial layer of the parotidgland infiltrates into the adjacent tissues. vessels and subcutaneous tissue. Thistumor has a cystic lesion which isregarded as necrosis.

IMAGING FINDINGS

In the imaging examination, emphasis was placed on the mannerof infiltration into the adjacent tissue and the internal homogeneity of the tumor. Cases 1 and 4 exhibited homogeneity withabsence of infiltration. The tumor margin was well defined in case1 and case 4 showed an ill-defined tumor margin with multipleprojections Table 2 . The tumors had rapidly increased in sizewithin 2 months incases 2, 3 and 5. All exhibited infiltration intothe adjacent vasculature, muscles and subcutaneous tissue andnecrosis or cystic changes of the internal structures, suspected tobe retention cysts Figs I and 2 .

TREATMENT

All subjects underwent surgical procedure. According to thespecific locations of the foci, superficial parotidectomy twocases or total parotidectomy one case was done. More recently,biopsies have been performed in two cases for intraoperativerapid pathological diagnosis the frozen section when malignantlymphoma was suspected. Cases 2, 3 and 5 underwent combination chemotherapy, such as with MACOpP or VEPA, followingsurgery. For radiotherapy, cobalt y-irradiation was employed forall subjects. Cases 3 and 4 were irradiated on the parotid gland

Jpn J Clin OncoI1998;28 4 7

Figure 2. CT image of case 5. The tumor infiltrates into adjacent tissues andvessels. This tumor has a cystic lesion which is regarded as necrosis or aretention cyst.

where the lesion was located and on the ipsilateral neck throughthe lateral portal. Case 1 was irradiated on the parotid gland,oropharynx and whole neck including through the parallelopposed lateral portals and antero-posterior portals. Cases 2 and5 were irradiated on both the parotid glands and oropharynx andon the neck from upper to middle through the parallel opposedlateral portals. The radiation dosage ranged from 40 to 44 Gydelivered at 1.8-2.0 Gy per fraction over 5weeks Table 3 .

CLINICAL COURSE

The patients have been followed for 2-8 years. No relapses haveoccurred and clinical courses were satisfactory for those in stageI cases 3-5 . After 8 months, a biopsy specimen showed relapseof the inguinal lymph nodes in case I, which was treated withchemotherapy. Since then, he has been alive and well for morethan 7 years. It should be noted that this patient did not initiallyundergo chemotherapy. MRI suggested a tumor relapse in thelymph node of the upper cervical region which had been treatedwith radiotherapy in case 2. The patient was subjected toadditional radiotherapy with 24 Gy of cobalt y-irradiationcombined with MACOP-P. Since then, no tumor relapse has beennoted at either this or other sites Table 4 .


4/5

8 Malignant lymphoma theparotid glandTable 3. Modalities of treatment

SPD +LND 60CoCase

2

3

4

5

Surgical procedure

Biopsy

Biopsy

SPD

Total resection

Source

CO

60Co

Radiation dose Gy Treatment method Field30 Opposed Primary lesion

antero-posterior whole neck14 Opposed lateral44 Opposed lateral Primary lesion

whole neck40 Lateral Primary lesion

upper neck40 Lateral Primary lesion

upper neck40 Opposed lateral Primary lesion

whole neck

Chemotherapy

MACOP-PVEPAMACOP-P

MACOP-P

SPD, superficial parotidectomy; LND, lymph node dissection.

Table 4. Outcome after treatmentCase Period of observation (months) Site of relapse Time of relapse

95 Lt. inguinal lymph node After 8 months2 83 Cervical lymph node After 2 months3 55 None4 25 None5 66 NoneNED, no evidence of disease.

TreatmentVEPA24 Gy,MACOP

Present stateNEDNEDNEDNEDNED

DISCUSSIONIt has been reported that 80-85 of parotid gland tumors arebenign and 15-20 are malignant (3). It is common knowledgethat tumors originating in theparotid gland arewithout characteristic features in their various imaging presentations and thatdifferentiation between benign and malignant tumors is difficult.However, some workers have reported that these tumors can bedifferentiated by tumor margins, tumor homogeneity, infiltrationinto the adjacent tissue and signal intensity inMRI. There are alsosome correlations between the malignancy seen in histopathological examinations and the fmdings from imaging studies(1,4-7). Malignant lymphoma originating in the parotid gland isrelatively rare and occurs in 1-5 of tumors where the parotidgland is the original site of the tumor (2). It iscommonly believedthat the differentiation of malignant lymphoma originating in theparotid gland from other tumors, including benign tumors, isdifficult; however, some authors have reported that malignantlymphomas showed tumor homogeneity surrounded by welldefmed margins and were rarely associated with necrosis (8,9).The observations of thepresent cases indicated that it is necessaryto consider thepossibility of malignant lymphoma even when thelesion rapidly increases in size and exhibits necrosis or aninfiltrative tendency in the imaging presentations, stronglysuggesting epithelial tumors.

In general, malignant lymphoma originating in the parotidgland is histologically described as low-grade non-Hodgkin slymphoma, frequently belongs to the B-cell type and rarelyrelapses into other sites (7,10-16). However, in thepresent series,two and one of the cases were classified as diffuse large cell typeand diffuse small cleaved immunoblastic type, respectively.These three exhibited a tendency to infiltrate the adjacent tissueand tumor inhomogeneity in the imaging findings, suggesting acorrelation with a histologically intermediate or high grade ofnon-Hodgkin s lymphoma. In the present series, it was successfully controlled by radiotherapy, with dosages ranging from 40 to44 Gy. The patients were followed for 2-8 years and no relapsewas found in the three patients with stage However, both stageII patients had relapses and were subjected to additionalradiotherapy combined with chemotherapy. Since then, no tumorrelapse has been noted at either this or other sites.Generally, most patients experience xerostomia if a substantial

part of the parotid glands is included within the radiation portal.Only one patient (case 1), who received 44 Gy in the bilateralparotid glands, developed mild dry mouth. However, theremaining four patients did not suffer from xerostomia. The lowincidence of xerostomia at the time of the last follow-up wasthought to be due tothe fact that the dosage of less than 44Gy onthe parotid glands did not cause irreversible depression of the


5/5

parotid function. Franzen et al. 17) reported that most patientswho received less than 52 Gy showed a recovery of secretionbeginning after 2 months with a continuous improvement of thesalivary flow up to 18 months. Also, Valdes Olmos et al. 18)reported that excretion was almost invariably impaired at doseshigher than 45 Gy, regardless of the time interval after radiotherapy.

Two patients underwent superficial parotidectomy and and onetotal parotidectomy. However, more recently, biopsies have beenperformed in two cases for intraoperative rapid pathologicaldiagnosis frozen section), as malignant lymphoma was suspected.In conclusion, malignant lymphoma including intermediate orhigh grade originating in the parotid gland indicated satisfactoryprognosis following radiotherapy and chemotherapy.

knowledgmentsThe authors thank Mr Robert Holmes Sapporo Medical University, Sapporo, Japan) for assistance with the manuscript and MsE. Sudou for secretarial assistance. This work was supported bygrants for Cancer Research from the Ministry of Education,Science and Culture M.H.), Japan.

eferen es1. FrelingNJM,MolenaarWM,VenneyA,MooyaartEL,PandersAK,AnnyasAA, et al. Malignant parotid tumors: clinical use of MR imaging andhistologic correlation. Radiology 1992;185:691-6.2. NagataM, KumazawaH, Iwai H, Momotani A, ShiraishiS, Yamashita T.Study of malignant lymphoma in the parotid gland region. NipponJibiinkouka Gakkai Kaiho 1996;99:918-25 in Japanese).

JpnJ Clin OncoI1998;28 4 93. BatsakisJG.Tumorof theHead and Neck,2ndedn. Baltimore: Williams andWilkins,1979;2-75.4. SwartzJD, Rothman MI, Marlowe FI, Berger AS. MRI of parotid masslesions: attemptsat histopathologic differentiation. J ComputAssistTomogr1989;13:789 C 96.5. Vog1 TJ,DreselSID,SpathM, GreversGO, Willirnzig CW,SchedelHK,etal. Parotid space: plain and gadolinium-enhanced MR imaging.Radiology1990;27:379-92.6. Som PM, Biller HF. High g rade malignancies o f the parotid sp ace:

identification with MRI.Radiology 1989;173:82 67. Tabor EK, CurtinHD. MR of the salivaryglands.RadiolClin NorthAm1989;27:379-92.8. HashidaI,TamakiY,SakuraiH,TakahashiT, MaebayashiK,HayakawaK,etal.Malignantlymphomaof the parotidgland:a studyof sixcases.GannnoRynsho 1995;41:863-7 in Japanese).9. HymanGA,WolffM.Malignantlymphomaofthe salivaryglands.AmJ ClinPathol1976;65:421-38.10. Jaco bs C , Ho ppe RT. Non-Hodgkin s lymphoma of head and neckextra-nodal sites.IntJ RadiatOncolBiolPhys 1985;U:357-64.II. BalmAJ, DelaereP,Hilgers l SomersR, VanHeerdeP.Primarylymphomaof mucosa associated lymphoid tissue MALT) in the parotid gland.ClinOtolaryngolI993;18:528-32.12. SchmidD, HelbronD, LennertK Primarymalignantlymphomas localizeinsalivaryglands.Histopathology 1982;16:673 8713. AmpilFL, MisraR Malignantlymphomaof the salivarygland:casereportsand reviewof the literature. RadiatMed 1987;15:20 614. Takahashi H, Tsuda N, Tezuka F, Fujita S, Okabe Non-Hodgkin slymphoma of the major salivary gland: a morphologic and immunohistochemicalstudyof 15cases.J OralPatholMed 1990;19:306 1215. HjorthL, Dommerby H, KruseS, NielsenA. Primarymalignantlymphomaof the salivaryglands.Tumori 1986;72:491 716. FurukawaM,OkabeY,UmedaR. Malignantlymphomaof theparotidgland.AurisNasusLarynx1982;9:165 7117. Franzen L, FunegardU, Ericson T, Henriksson R. Parotid gland functionduringand following radiotherapyof malignanciesin thehead and neck. Aconsecutive study of salivary flow and patient discomfort. Eur J Cancer1992;28:457-62.18. Valdes OlmosRA,Keus RB, TakesRP,vanTinterenH, BarisFJ,HoefnagelCA, et al. Scintigraphic assessment of salivary function and excretionresponse in radiation-induced injury of the major salivary glands. Cancer1994;73:2886-93.

diagnosis and treatment of malignant lymphoma

Documents