malignant warthin's tumour: ultrastructural study

J Clin Pathol 1984;37:170-175

Malignant Warthin's tumour: an ultrastructural studyLAURENCE JR BROWN, SAMUEL R APARICIO

From the Department ofPathology, University ofLeeds, and Electronmicroscopy Unit, Clinical SciencesBuilding, St James's Hospital, Leeds

SUMMARY Undifferentiated malignant cells in a Warthin' s tumour (adenolymphoma) were

studied by light and electron microscopy. The ultrastructure of these cells indicated that theywere poorly differentiated adenocarcinoma arising from the glandular component of theWarthin's tumour. Some differences between this case and previous ultrastructural studies are

described.

Warthin's tumour (adenolymphoma, papillary cys-tadenoma lymphomatosum) is an uncommontumour which is found predominantly in men,usually affecting the parotid gland. Malignantchange is rare.' 2 There have been two previousultrastructural studies, only one of which dealt withmalignant change.34 The case presented here is of amalignant Warthin's tumour, which by light andelectron microscopy showed some differences topreviously reported material.

Case report

A 68 year old woman presented with a unilateral,symptomless, slowly growing swelling at the angle ofthe left side of her jaw, which had been present fortwo years. Further examination, including computedtomography of the head and thorax, did not showany coexistent neoplasm. Biopsy of an enlargedhomolateral posterior triangle lymph node indicateda malignant Warthin's tumour, and the patient wasreadmitted for definitive excision. At operation theswelling had enlarged since the first examination andwas a hard fixed mass covering an area measuring3 cm x 2 cm at the angle of the left jaw. Tumourcells were infiltrating into the upper posteriortriangle lymph nodes, and most of the lesion wasremoved by a major neck dissection. The patientreceived postoperative radiotherapy, and two yearsafter the initial diagnosis there has been no recurr-ence.

METHODSSpecimens were fixed in buffered formalin, routinelywax processed, and sections were stained withhaematoxylin and eosin, periodic acid Schiff, alcianblue, Masson-Fontana, Schmorl's and for reticulin.

Accepted for publication 8 November 1983

Representative blocks from the formalin fixedmaterial were routinely processed for electron mic-roscopy, and ultrathin sections were examined usinga JEOL 100S transmission electron microsope atmagnifications ranging from x 500 to x 20 000.

RESULTSGross pathologyThe specimen removed at operation was a friableand partly cystic nodule of cream coloured tissuemeasuring 1-8 cm x 2-2 cm x 1.5 cm. No separatelymph nodes were identified.

Light microscopyBoth the biopsy specimen and the operative speci-men showed the typical lymphoid and epithelialelements of an adenolymphoma but with islands oflarge anaplastic tumour cells within the lymphoidstroma (Fig. 1). The nuclei of the epithelial cellswere mostly regular and arranged in orderly doublelayers, but there were a few areas where there wasglandular hyperplasia leading to a cribriform patternwith anisocytosis and nuclear pleomorphism. Theseareas were thought to be dysplastic and thereforeregarded as transitional areas between the benignand malignant components.The cytologically malignant cells were distributed

singly or arranged in irregular groups within thelymphoid stroma. These cells were large, pale, andpolygonal, showing an increased nuclear-cytoplasmic ratio. Nuclei were pale and vesicular,pleomorphic, had a variable chromatin pattern withlarge amounts of euchromatin, a high mitotic rate(11/100 high power field), and slightly eosinophilicnucleoli (Fig. 1). The cells did not stain with periodicacid Schiff, alcian blue, Masson-Fontana, orSchmorl's. Compared with the benign epithelium,the granularity and eosinophilia of the cytoplasmwere less pronounced and more focally distributedwithin the cell. Malignant cells extended in an

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Malignant Warthin's tumour: an ultrastructural study

Fig. 1 Anaplastic large cellsinfitrate the lymphoid stromaof the adenolymphoma; anabnormal mitosis is seen atcentre bottom. Haematoxylinand eosin x400.

infiltrative pattern to the limits of the surgical exci-sion.

Electron microscopyThe epithelial cells of the adenolymphoma weresmall (typically 15 ,um x 7 ,m) and regular withfairly uniform sometimes crenated nuclei (5,umdiameter) (Fig. 2). The cytoplasm was packed withnumerous round or slightly oval mitochondria from0 3 ,um to 1 0,um in diameter, some of which hadabundant parallel linear cristae. Certain mitochon-dria showed aggregation of the cristae to formsheaves (Fig. 3). Other organelles seen were secret-ory vesicles, liposomes, lysosomes, small amounts ofrough endoplasmic reticulum, and profiles of Golgiapparatus. Moderate numbers of intermediatefilaments, some of which were arranged in bundles,were present. Epithelial features such as junctionalcomplexes, a terminal web, complex interdigitatingcell membranes, desmosomes, apical microvilli, anda basement membrane with hemidesmosomes wereall evident (Fig. 3). Several apoptotic cells wereassociated with the epithelial component, but therewas no evidence for two cell populations (Fig. 2).The anaplastic cells showed some or all of the

foregoing features in a variable and less organisedpattern. They were much larger (up to 30 ,um) andhad large randomly orientated, irregularly shapednuclei (up to 15 ,mm diameter) (Fig. 2). Smallamounts of heterochromatin were present, andthere were up to two large (2.5 gm diameter) nuc-

leoli. The mitochondria were variable in size andsparsely distributed in the cytoplasm but neverthe-less were similar to those of the benign epithelium inthat they had numerous parallel cristae which wereoccasionally arranged in sheaves (Fig. 4). Multiplesecretory vesicles, lysosomes, and a few intracyto-plasmic lumina were seen. In addition, some of theanaplastic cells contained clear lipid vacuoles, oftenclustered in variably sized groups (Fig. 2). Inter-mediate filaments and complex interdigitating cellmembranes similar to those seen in the benign com-ponent were a feature of the anaplastic cells (Fig. 4).Desmosomes and poorly formed hemidesmosomeswere present, but keratohyaline granules and base-ment membrane like material could not beidentified. A few of the malignant cells werearranged into microacini (Fig. 5). These cellsshowed a clear apical zone, stunted microvilli, anddirectional organisation of the organelles.The stroma contained more plasma cells than had

been apparent on light microscopy, but no differ-ences in the stroma associated with either the benignor malignant components could be detected (Fig. 5).

Discussion

There have been reports of the following arising inadenolymphoma: adenocarcinoma,58 squamouscarcinoma,9-" and mucoepidermoid carcinoma.'2- 14In a recent paper Krogdal and Bretlau'5 report acase of adenocarcinoma developing in an

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Fig. 2 Low magnificationelectron micrograph showing acord ofanaplastic cells adjacentto an epithelial cleft oftheadenolymphoma (right ofcentre)containing apoptotic debris in thelumen. x2000.

adenolymphoma and give a critical view of the pub-lished work.

In the present case, light microscopy showed thetypical histology of an adenolymphoma and islandsof anaplastic tumour cells scattered among andinfiltrating the adenolymphoma. Areas of epithelialhyperplasia and dysplasia where the cells werearranged in cribriform sheets were interpreted as aprogression from benign epithelium through dys-plasia to poorly differentiated carcinoma.Of the two previous ultrastructural studies of an

adenolymphoma34 only one4 dealt with malignantchange. Using electron microscopy we have showngeneral epithelial similarities between the benignepithelium and malignant component such asdesmosomes, hemidesmosomes, interdigitating cellmembranes, and microvilli. Secretory vesicles, Golgiapparatus, a terminal web, acinus formation,intracellular lumina, and directional organisation of

organelles in the malignant cells are taken to indi-cate glandular rather than squamous differentiation.Absence of keratohyaline granules would tend toconfirm this. In addition, the similarities inmitochondrial morphology, especially the arrange-ment of the cristae into sheaves, indicate origin fromthe salivary gland epithelium of the adenolym-phoma.The previous ultrastructural studies34 detailed

two populations of cells forming the epithelium ofthe adenolymphoma. We could not confirm this, butwe have described an appreciable population ofapoptotic cells, which has not been reported previ-ously.

In Ackerman's Surgical Pathology 16 it is suggestedthat adenolymphomas are benign; this case andothers,4-'I5 however, show that the lesion iscapable of malignant transformation, albeit rarely.The ultrastructral features strongly suggest that the

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Malignant Warthin's tumour: an ultrastructural study 173

Fig. 3 Details ofthe cytoplasmof three benign epithelial cells,limited by a basal lamina (top).Several desmosomes (D),hemidesmosomes (H), andmitochondria with sheaves ofcristae (arrows) are seen.EM x12 000.

Fig. 4 Cytoplasmic details oftwo adjacent malignant epithelialcells. Interdigitating cell borders(left of centre) and several thinbundles ofintermediate fiamentsare seen. The two largestmitochondria in the field showarrangement of cristae similar tothat seen in Fig. 3. EM x12 000.

.,.Pqw

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*:,* t>-f

malignant cells have derived from the glandularcomponent and in this case have given rise to anadenocarcinoma. Moreover, unlike previouscases,69 14 no other prior or coexistent primarymalignancy which could have metastasised to theparotid was found. The malignant adenolymphoma

= Fig. 5 Anaplastic cells;̂?t R showing acinar arrangementW= :W.>* ;$ N-_1 with narrow lumina at arrows.

Stroma with plasma cells atbottom left. EM x2000. Inset:

- ys.R<;i2<ht ie detail ofone lumen withmicrovilli in the centre. EMx20 000.

itself has been said to metastasise in fivereportsi '-_

and on occasion to cause death between three and10 years578 later. In common with several othercases described4"'3 distant metastasis has notoccurred in our patient and she remains well twoyears after presentation. Therefore, the prognosis of

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Malignanzt Warthin's tumour: an ultrastructural study

malignant adenolymphoma seems to be difficult topredict, but in this case it appears to behave in anindolent manner.

We are grateful to Professor G R Giles for allowingus to use the clinical material relevant to this case.

References

'Warthin AS. Papillary cystadenoma lymphomatosum. A rareteratoid of the parotid region. J Cancer Res 1929; 13: 116-25.

2 Foote FW, Frazell EL. Tumours of the major salivary glands.Atlas of tumour pathology, Vol II. Washington DC: ArmedForces Institute of Pathology, 1954:129-36.

Gavran MH. The ultrastructure of papillary cystadenomalymphomatosum of the parotid gland. Virchow Arch PatholAnat 1965;338: 195-202.

4Moosavi M, Ryan CK, Schwartz S, Donnelly JA. Malignantadenolymphoma. Human Pathol 1980; 11: 80-3.

Reubner B, Bramall JL. Malignant papillary cystadenomalymphomatosum. AMA Arch Pathol 1980;69:110-7.

6 Little JW, Rickles NH. Malignant papillary cystadenomalymphomatosum. Cancer 1961;18:790-4.

7Dobrossy L, Ronay D, Molnir C. Malignant papillarycystadenoma lymphomatosum. Oncology 1972;26:457-65.

1758 Kessler E, Koznizky IL, Schinder J. Malignant Warthin's

tumour. Oral Surg 1977;43: 111-5.De La Pava S, Knutson GH, Moktar F, Pickren JW. Squamous

cell carcinoma arising in a Warthin' s tumour of the parotidgland. Cancer 1965;18:790-4.

'° Assor D. Bilateral carcinoma of the parotid, one cancer arisingwithin a Warthin's tumour. Am J Clin Pathol 1974;61: 270-4.

Baker M, Yuzon D, Baker B. Squamous cell carcinoma arising inbenign adenolymphoma (Warthin's tumour) of the parotidgland. J Surg Oncol 1980;15:7-10.

12 Tanaka N, Chen WC. A case of bilateral papillary cystadenomalymphomatosum (Warthin's tumour) of the parotid compli-cated with muco-epidermoid tumour. Gan 1953;44:224-31.

3 Gadient SE, Kalfayan B. Muco-epidermoid carcinoma arisingwithin a Warthin's tumour. Oral Surg 1975;40:391-8.

i4 Lumeran H, Freedman P, Caracciolo P, Remigio PS. Synchronousmalignant muco-epidennoid tumour of the parotid gland andWarthin's tumour in adjacent lymph node. Oral Surg1975;43:953-8.

Krogdahl AS, Bretlau P. Malignant transformation of adenolym-phomas. Ann Otol Rhinol 1983;92:49-52.

16 Rosai J. Ackerman's surgical pathology, 6th ed. London: CVMosby Company, 1981:577-9.

Requests for reprints to: Dr LJR Brown, Department ofPathology, University of Leeds, Leeds, England



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