5JClin Pathol 1996;49:524-526

Collision tumour of the oesophagus: a challengefor histological diagnosis

W K Ng, KY Lam, A C L Chan,Y L Kwong

AbstractAn unusual case ofmantle cell lymphomametastasising to squamous cell carcinomaofthe oesophagus, in a 62 year old Chineseman, is reported. A histological diagnosisbased on examination of a small endo-scopic biopsy specimen, in the absence ofdetailed clinical information, may bedifficult, as the lymphoma component can

be mistaken for reactive lymphoid infil-trate which is sometimes present adjacentto squamous cell carcinoma. Correlationwith the clinical history, careful assess-

ment of the subtle histological changes,and use of ancillary methods such as

immunohistochemistry are most helpfulin making the correct diagnosis. This case

also illustrates further the possible occur-

rence of lymphomatous infiltrates sur-

rounding other lesions in patients with a

previous or concurrent history of lym-phoma.(J Clin Pathol 1996;49:524-526)

Keywords: oesophagus, squamous cell carcinoma, lym-phoma.

Department ofPathology,University ofHongKong,Queen Mary Hospital,Hong KongWKNgKY LamA C L Chan

Department ofMedicineY L Kwong

Correspondence to:DrW K Ng,Department of Pathology,Queen Mary HospitalCompound,Pokfulam Road, Hong Kong.

Accepted for publication24 April 1995

Various collision tumours, which are defined as

the concrescence of two neighbouring inde-pendent neoplasms, have been described in thegastrointestinal tract. Examples may includesquamous cell carcinoma and leiomyoma ofthe oesophagus,' adenocarcinoma and lym-phoma of the stomach,2 adenocarcinoma andcarcinoid tumour of the stomach,89 adenocar-cinoma and lymphoma of the small intestine,10and adenocarcinoma and lymphoma of therectum." Many of these tumours were diag-nosed on examination of the excised surgicalspecimens, with the second tumour beingdiscovered as an incidental finding. Here, we

describe a rare case of oesophageal "collision"tumour composed of squamous cell carcinomaand mantle cell lymphoma. The two compo-nents, however, were not truly synchronousprimary tumours as the mantle cell lymphomametastasised to primary squamous cell carci-noma of the oesophagus. To the best of our

knowledge, this case is the first report in theliterature of squamous cell carcinoma coexist-ing with malignant lymphoma in the oesopha-gus. Moreover, our case was initially diagnosedon the basis of endoscopic biopsy. Thehistological diagnosis of this lesion based on

examination of a small biopsy specimen, in theabsence of detailed clinical information, maybe difficult. The malignant lymphoid compo-nent may mimic the reactive lymphocytic infil-trate which is sometimes present in the stroma

of ordinary squamous cell carcinoma of theoesophagus." This is especially true for lowgrade non-Hodgkin's lymphoma, in which thecytological atypia of malignant lymphoid cellsare subtle and may easily be missed.

Case reportThe patient, a 62 year old Chinese man, firstpresented to Queen Mary Hospital in 1991with conjunctival nodules, hard palate mass,and bilateral cervical lymphadenopathy. Biopsyat that time revealed non-Hodgkin's lym-phoma. Chest x ray, barium studies of the gas-trointestinal tract, and a computed tomo-graphy scan of the abdomen did not revealother sites of lymphoma involvement. Bonemarrow examination was unremarkable. Theclinical staging at that time was IIB. Thepatient was treated with nine monthly coursesof cyclophosphamide (400 mg/m' orally forfive days), vincristine (1.4 mg/m' intrave-nously) and prednisolone (100 mg/M2 orallyfor seven days), and achieved clinical remis-sion.

In 1995 the patient presented again withdysphagia and regurgitation. Solid food couldstill be tolerated, and there was no significantloss of weight or appetite. Physical examinationwas unremarkable and no superficial lymphad-enopathy or organomegaly was found. Bariumswallow showed an oesophageal lesion at thelevel of the T6 and T7 vertebrae. Upper endo-scopy revealed a right nasopharyngeal lesionand a tumour growth at middle third of theoesophagus. Biopsy specimens of the rightnasopharyngeal lesion and the oesophagealtumour revealed mantle cell lymphoma andmixed squamous cell carcinoma/mantle celllymphoma, respectively. The previous biopsyspecimens of conjunctival nodules and cervicallymph nodes were reviewed and showedsimilar features of mantle cell lymphoma. Thepatient was then treated with four monthlycourses of intravenous cyclophosphamide (750mg/M2), epirubicin (50 mg/m'), vincristine (1.4mg/M2), and oral prednisolone (100 mg/M2 forfive days). The oesophageal malignant lym-phoma apparently regressed on follow upendoscopy, although the carcinoma compo-nent was still present. The patient then under-went three-phase oesophagectomy. Intraopera-tively, the oesophageal tumour was seeninfiltrating into the left main bronchus. Thesubcarinal lymph node was enlarged. Histo-logical examination of the resected specimenconfirmed the presence of squamous cell carci-noma and residual mantle cell lymphoma. Thepostoperative course was uneventful. Furtherchemotherapy was planned after full convales-cence.

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Collision tumour of the oesophagus

r, ~ ~~~~~~~~~~fFigure 1 High power photomicrograph of the mantle cell lymphoma showing the subtlecytological changes. Note the irregular and occasionally cleaved nuclei containing finechromatin. (Haematoxylin and eosin, x5OO.)

The initial, fresh oesophageal endoscopicbiopsy specimen was submitted for examina-tion. Half of the specimen was frozen forsubsequent immunohistochemical studies andthe other half was promptly fixed in 10% neu-

tral formalin and embedded in paraffin wax.

Sections, 3 gim thick, were cut and stained withhaematoxylin and eosin, Gordon and Sweets'silver, periodic acid Schiff, and methyl greenpyronin stains. Immunohistochemistry was

carried out on the frozen tissue using theStreptavidin-biotin complex technique forCD5 (Dako, Glostrup, Denmark), CD23(Dako), immunoglobulins (IgD from Dako,IgG from Biotest Diagnostic, and IgM fromBiotest Diagnostic), K and X light chains (Bec-ton Dickinson), and a panel of B (CD 19 fromBecton Dickinson and CD22 from Dako) andT cell markers (CD3 from Becton Dickinson).The oesophagectomy specimen was also pro-cessed similarly after representative blockswere sampled from the fresh tissue. Macro-scopically, the oesophageal tumour was an

ulcerative growth, situated 6.5 cm proximal tothe gastro-oesophageal junction, measuring 9cm at its widest point.

Figure 2 Photomicrograph of the oesophagectomy specimen showing primary squamouscell carcinoma and residual mantle cell lymphoma. (Haematoxylin and eosin, x40.)

HISTOLOGYHistological examination of the endoscopicbiopsy revealed several tiny fragments ofoesophageal mucosa with severe dysplasia ofthe surface squamous epithelium with focalsuggestion of stromal invasion. In one of thetissue fragments, several clusters of lymphoidaggregates, composed mainly of a monotonouspopulation of small lymphoid cells, werepresent. The cells had irregular nuclear mem-brane and scanty cytoplasm (fig 1). Thecytological features were similar to those of theprevious conjunctival and cervical lymph nodebiopsy specimens. Immunohistochemical studiesshowed that these lymphoid cells were positivefor CD5, CD19 and CD22, but negative forCD3 and CD23. Surface IgD and IgM, as wellas K light chain restriction, were demonstrated.A diagnosis of squamous cell carcinoma of theoesophagus coexisting with mantle cell lym-phoma was made.The histological diagnosis was subsequently

confirmed by examination of the oesophagec-tomy specimen. The excised specimen showeda moderately differentiated squamous cell car-cinoma of the oesophagus with transmuralinfiltration. Keratin pearl formation was fre-quently found. Vague nodules of small malig-nant lymphoid cells were also present in thesubmucosa, muscularis propria and adventitialsoft tissue, representative of residual mantlecell lymphoma (fig 2).

DiscussionHistological diagnosis of squamous cell carci-noma and lymphoma of the oesophagus basedon examination of a small endoscopic biopsyspecimen may be difficult, especially if thelymphoma component is of low to intermedi-ate grade and detailed clinical information isnot available. Assessment of the lymphoidcomponent based on cytological atypia alone issubjective and may not be conclusive. The useof immunohistochemistry and, most impor-tantly, correlation with the clinical history isnecessary if the correct histological diagnosis isto be made.

In general, B cell non-Hodgkin's lymphomais characterised by a monotonous populationof malignant lymphoid cells, in contrast to thepolymorphous cell population seen in reactivelymphoid infiltrate. Germinal centres with welldefined mantle zones are not seen. As formantle cell lymphoma,"3 the tumour cells aresmall to medium in size and contain irregularand occasionally cleaved nuclei, fine chroma-tin, small nucleoli, and scanty cytoplasm. Thenuclei are paler compared with those of smalllymphocytic lymphoma.The tumour may grow in diffuse and some-

times vaguely nodular patterns. Hyaline depos-its may be seen around small capillaries. Thickreticulin fibres forming a coarse alveolarnetwork surrounding large solid group oftumour cells may also be found. The monoto-nous cell population, absence of germinal cen-tre, and the subtle cytological changes raise thepossibility of a diagnosis of B cell non-Hodgkin's lymphoma; subsequent investiga-

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Ng, Lam, Chan, Kwong

tions including immunohistochemical analysesmust be carried out before the final conclusionis drawn.

Immunohistochemically,1"'7 mantle celllymphoma, which is probably derived from fol-licular mantle lymphocytes," is characteristi-cally CD5 positive and CD23 negative. OtherB cell markers, such as CD 19, CD20 andCD22, are also positive. The tumour cells mayalso express surface immunoglobulin, usuallyIgM and sometimes IgD. The monoclonality ofthe malignant B cells can be confirmed bydemonstrating light chain restriction. Unfortu-nately, some of these antibodies-for example,CD5 and CD23, are more suitable for cryostatsections; and the demonstration of light chainrestriction is often not satisfactory on paraffinwax sections. In controversial cases, demon-stration of immunoglobulin gene rearrange-

ment by molecular biological techniques may

be needed as a last resort.The coexistence of squamous cell carcinoma

and mantle cell lymphoma in this case is mostlikely coincidental, with unrelated aetiologies.The squamous cell carcinoma component isthe primary, while the lymphoma represents a

metastatic lesion, probably originating fromthe cervical lymph node. This is, however, incontrast to the truly synchronous primary lym-phoma and adenocarcinoma of stomach, inwhich Helicobacter pylori may be of some aetio-logical significance.19-23

In summary, our case represents an unusualexample of lymphoma metastasising to squa-

mous cell carcinoma of the oesophagus. Thisposes a diagnostic challenge to histopatholo-gists and further illustrates the importance of a

detailed clinical history. Clinical histopatholo-gists must alert clinicians to the possibleoccurrence of lymphomatous infiltrates sur-

rounding other primary lesions in patients witha previous or concurrent history of lymphoma.This is especially true for those patients withlymphoma presenting with a high clinicalstage. Careful assessment of the subtle histo-logical changes and the use of ancillarymethods such as immunohistochemistry andmolecular biology is essential before the finalconclusion is drawn.

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