primary dysphagia: two case

Gut 1993; 34:994-998

CASE REPORTS

Isolated primary oesophageal involvement bylymphoma: a rare cause of dysphagia: two case

histories and a review of other published data

B G Taal, P Van Heerde, R Somers

The Netherlands CancerInstitute, Department ofMedical Oncology,Amsterdam, TheNetherlandsB G TaalP Van HeerdeR SomersCorrespondence to:B G Taal, MD, TheNetherlands Cancer Institute,Department of MedicalOncology, Plesmanlaan 121,1066 CX Amsterdam, TheNetherlands.Accepted for publication11 November 1992

AbstractPrimary oesophageal involvement by lymph-oma in two patients, one with Hodgkin'sdisease and one with non-Hodgkin's lymph-oma is reported. In both, there were nomanifestations of the disease outside theoesophagus, which is exceptionaily rare. In thepatient with non-Hodgkin's lymphoma, theoesophageal tumour was the first manifesta-tion of lymphoma. Shortly after admission hedeveloped a tracheo-oesophageal fistula fromwhich he died before treatment could bestarted. In the patient with Hodgkin's disease,isolated oesophageal lymphoma was the firstrelapse after a 13 year interval free of disease.As he had previously received mediastinalirradiation he was treated with combinationchemotherapy that resulted in long termsurvival (>five years). Several other long termsurvivors have been described but only afterradiotherapy or surgery. These findingssuggest that systemic chemotherapy may beequally successful in treating isolated primaryoesophageal lymphoma, thus offering analternative for those patients in whom localtreatment is contraindicated.(Gut 1993; 34: 994-998)

Lymphomatous involvement of the oewall is rare. According to published st

Figure 1: Case I (non-Hodgkin's lymphoma): barium swallow at presentation (A ashowing irregular narrowing and ulceration ofthe oesophagus; shortly aftervards aoesophagealfistula developed (C).

mainly associated with Hodgkin's disease, whereit has been reported in up to 6% of cases inpostmortem studies; the incidence ofoesophagealinvasion by non-Hodgkin's lymphoma does notexceed 1-6%.'2 Since 1935, only 90 cases ofoesophageal lymphoma (53 Hodgkin's disease,37 non-Hodgkin's lymphoma) have been des-cribed worldwide. 1-18

In most patients, secondary involvement as aresult of enlarged mediastinal lymph nodes waseither shown or implied. Primary involvement,however, defined as lymphoma developing in theoesophageal wall itself, seems to be exceptionallyrare, especially in its isolated form: we have beenable to identify only six cases in which patientspresented with oesophageal tumour as the onlymanifestation of lymphoma (five Hodgkin'sdisease, one non-Hodgkin's lymphoma).? 48 1617

In this report we present two other patientsfrom The Netherlands Cancer Institute withisolated primary oesophageal involvement bylymphoma. Their case histories show the diag-nostic problems that may be associated with thisdisease.

Case 1In September 1976 a 59 year old man wasadmitted to a local hospital for evaluation of

sophageal intermittent complaints of retrosternal painadies, it is related to the ingestion of food, but sometimes

also occurring at night. Barium swallow showedan irregular mucosal pattern in the midoeso-phagus. Endoscopy disclosed abnormal mucosaat 26 cm from the incisors; biopsies showedchronic inflammation.While being evaluated for dysphagia he

developed symptoms of intestinal obstructionwith severe vomiting, caused by a large tumourin the sigmoid colon. A negative metastaticsurvey was followed by resection. Pathologicalexamination showed a Dukes's C adenocar-cinoma. The patient made an excellent recoveryfrom this operation. Apart from relief of intes-tinal obstruction he also experienced relief ofdysphagia that supported the hypothesis thatoesophagitis had developed secondary to vomit-ing in the presence of large bowel obstruction.He enjoyed good health until his initial com-

nd B) plaints recurred one year later. Apart frombroncho- retrosternal pain and discomfort there were also

complaints of fatigue, anorexia, and intermittent

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Isolated prima?y oesophageal involvement by lymphoma: a rare cause ofdysphagia: two case histories and a review ofotherpublished data

A,4:sw

Figure 2: Case I (non-Hodgkin's lymphoma): malignant lymphoma, diffuse, predominantlysmall cleaved and centroblastic centrocytic; some plasmacytoid features. Haematoxylin andeosin; top originally x250; bottom originally x400.

fever. No abnormalities were found on clinicalexamination. Blood tests were normal with theexception of a slightly raised erythrocytesedimentation rate. Barium swallow showedmidoesophageal ulceration (Fig 1). Again,biopsies showed only chronic inflammation.Afterwards, oesophagoscopy was repeated twiceas he failed to respond to conservative manage-ment. After a third attempt at oesophogoscopy inMarch 1978 a picture consistent with non-

Hodgkin's lymphoma was found. The patientwas referred to our hospital for further evalua-tion and treatment.Endoscopy showed two small tumours at 21

cm from the incisors and a pedunculated polyp at34 cm. Biopsies were positive for malignancy atboth positions, defined as non-Hodgkin'slymphoma (Fig 2), mainly small cleaved accord-ing to the Working Formulation (1982), mainlycentrocytic with the Kiel classification (1988).Routine staging procedures showed no mani-festations of lymphoma outside the oesophagus,so a diagnosis of stage I extranodal non-

Hodgkin's lymphoma was made. Radiotherapywas considered the best option for treatment butbefore this could be started, rapidly progressivedyspnoea developed. Bronchoscopy showed a

narrowed left main bronchus apparently due totumour compression. As an emergency measure,chemotherapy was applied (10 mg mitoxine,2 mg vincristine, and 100 mg prednisolone).Further problems emerged the next day when abarium swallow (Fig 1) showed a broncho-oesophageal fistula, which was treated withantibiotics, a nasogastric tube for continuoussuction, and a gastrostomy for feeding.

Further radiotherapy was cancelled, as theclinical condition of the patient deterioratedrapidly; he died from septic shock three weeksafter admission. Necropsy disclosed malignantlymphoma in the distal 15 cm of the oesophagusassociated with extensive fistula formation,mainly to the left main bronchus. Microscopyconfirmed earlier findings. No manifestations oflymphoma were found outside the oesophagus.

Case 2In June 1986, a 34 year old man presented with athree month history of progressive dysphagiaand an associated weight loss of 10 kg. Onadmission he was unable to swallow anything butliquids and mashed solids. Thirteen years earlierhe had been treated in our hospital for stage IIAnodular sclerosing Hodgkin's disease withpathological lymph nodes in the left supra-clavicular region, both axillary regions, and themediastinum. He was treated with irradiation:mantle field 40 Gy, submantle region 35 Gy,para-aortic region and spleen 40 Gy. A completeremission had been achieved; follow up wasuneventful until current admission. Apart fromdysphagia there were no complaints of nightsweats, fever, or pruritus. A chest x ray film andphysical examination were normal. Althougherythrocyte sedimentation rate and alkalinephosphatase were slightly raised the otherrelevant laboratory values, including lactatedehydrogenase, were within normal limits.Barium swallow showed severe stenosis of the

distal oesophagus of about 8 cm in lengthassociated with polypoid mucosal lesions.Computed tomography scanning showed malig-nant involvement of 12 cm of the oesophaguswith infiltration of the aortic arch (Fig 3).Endoscopy showed a stricture with friablemucosa and ulceration, 7 cm long, at 28 cm fromthe incisors. Biopsies showed chronic inflamma-tion but no evidence of malignancy. This wassurprising: in our experience, patients with ahistory of mediastinal irradiation are at risk fordeveloping a squamous cell carcinoma of theoesophagus and the clinical picture was highlysuggestive of this type of malignancy. Afterrepeated biopsies, evidence of malignancy wasfound. Contrary to our expectations, microscopyshowed recurrent Hodgkin's disease. The mono-nuclear Hodgkin's cells and binuclear SternbergReed cells (Figs 4 and 5) showed the followingimmune marker pattern: CD 30 (syn BerH2,Kil) and CD 15 (syn Leu ml) positive; LCAMTl, UCML1, L26, MB1, and MB2 negative.Staging bone marrow biopsy and CT scanning ofthe mediastinum showed no extraoesophagealmanifestations of lymphoma. Endoscopic ultra-sonography was attempted but the instrumentcould not be passed through the stenotic area.

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Taal, Van Heerde, Somers

Figure 3: Case 2 (Hodgkin's disease): Computed tomography scan ofthe mediastinum. Top: atpresentation showing a circular oesophageal tumour, possibly invading the aortic arch, no

pathological lymph nodes. Middle: after 8xMOPP showing only slight residual thickening ofthe oesophageal wall at the level ofthe carina. Bottom: showing normal appearance oftheoesophagus fouryears after diagnosis. MOPP=mitoxine, vincristine, procarbazine,prednisolone.

Based on these findings, extranodal recurrence

of Hodgkin's disease, limited to the oesophagealwall, was considered to be the most likelydiagnosis.

Radiotherapy was, at most, only a limitedoption in view of the dose applied to themediastinal area in 1973. We decided to treat the

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patient with combination chemotherapy (MOPP=mitoxin, vincristine, procarbazine, andprednisolone). In response to the first cycle,dysphagia improved dramatically. After thesecond course he was back on a normal diet,gaining weight rapidly. A repeated bariumswallow showed almost complete disappearanceof the tumour; only a slightly narrowed segmentwith a length of 2 cm remained at the level of thecarina (Figs 6 and 7). Endoscopic ultrasono-graphy, successfully performed on this occasion,showed that this was due to minor local thicken-ing of the oesophageal wall.The radiological appearance of this area after

eight cycles was virtually unchanged; a CT scanwas compatible with either a small tumourremnant or fibrosis.As originally planned, MOPP was discon-

tinued at this stage; even assuming that tumourwas still present, a further reduction of itsvolume as a result of more than eight cycles wasconsidered unlikely.

Follow up was uneventful; CT scans con-tinued to improve until finally, four years later,the aspect of the oesophageal wall was com-pletely normal. Now, almost six years afterpresentation, this patient is alive and well withno signs of recurrence.

DiscussionOesophageal involvement by lymphoma is, inmost cases, secondary. Affected mediastinallymph nodes may either cause narrowing of thelumen due to external compression or the oeso-phageal wall may be invaded directly whentumours spread beyond their anatomicalboundaries. Primary involvement, defined aslymphoma developing in the oesophageal wallitself, is rare, especially in its isolated form whenit is the only focus of the disease.

Including our two patients, only eight cases ofisolated primary oesophageal involvement bylymphoma have been published."' 1617 Tables Iand II summarise their main characteristics.As shown, recurrence of Hodgkin's disease,

10 or more years after initial treatment for thiscondition, was diagnosed in most cases. Thenodular sclerosing form was the dominant histo-logical sybtype, although this was not specifiedin all patients.

Isolated primary non-Hodgkin's lymphoma ofthe oesophagus seems to be exceptionally rare; inboth reported cases, oesophageal lesions werethe first manifestation of the disease. Presentingsymptoms were not specific as neither patientinitially complained of dysphagia.An atypical presentation may contribute to a

diagnostic delay, although this also occurred inpatients with more specific symptoms. Diagnos-tic difficulties in those cases were related toconfusing radiological and endoscopic appear-ances or failure to obtain histological confirma-tion of lymphoma.A picture at barium swallow typical of malig-

nancy, similar to that described in our case 2patient, was only reported by Berman et al.'6Other authors were confronted with a muchmore puzzling radiological picture, especially inearly stages of the disease: a nodular aspect or

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Isolated primary oesophageal involvement by lymphoma: a rare cause ofdysphagia: two case histories and a review ofotherpublished data

Figure 5: Case 2 (Hodgkin's disease): most ofthe atypical cells are reactive CDIS (Leu Ml):membranous or cytoplasmic dark staining. Immunoperoxidase x 125.

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Figure 6: Case 2 (Hodgkin's disease): barium swallow at presentation (previous mediastinalirradiationfor Hodgkin's disease stage IIA) showing irregular narrowing ofthe oesophagus andpolypoid mucosal lesions, indicating carcinoma (A, B, and C). Considerable improvement aftertwo cycles ofMOPP (D and E). MOPP=mitoxine, vincristine, procarbazine, prednisolone.

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Figure 7: Case 2 (Hodgkin's disease): barium swallow at presentation (A), after twoyears (B),fouryears (C), andfive (D)years; it shows only minor residual stenosis due tofibrosis.

irregular narrowing of the oesophagus due tosubmucosal tumours was mentioned most oftenand interpreted as either peptic stricture,radiation stricture, or external compres-sion.8I5

Such interpretations seemed justified as allinitial biopsies, with one exception,4 were nega-tive, indicating either no abnormalities or merelychronic inflammation. Eventually the correctdiagnosis was made in seven patients afterrepeated endoscopic biopsies (case 1 and 2,Hambly and Blundell8), open biopsy3 or exami-nation or surgical specimens.2 1617

Negative endoscopic biopsies can, to someextent, be explained by the specific growthpattern of the tumour; primary lymphoma arisesin submucosal lymphoid patches, hence notwithin easy reach of biopsy forceps. Accessibilitymay improve when the tumour grows towardsthe oesophageal lumen, but matters becomemore complicated when growth is primarilydirected in the opposite direction, towards thesurface. Fistula formation - for example to thetrachea - may then be the first sign of the truenature of the disease.

Radiological and endoscopic appearances aremainly dependent on the presence of intra-luminal lesions. Submucosal swelling may belocalised, circumferential, or multifocal, resem-bling benign conditions like fibrotic strictures,leiomyoma, achalasia, or varices. Polyps orpapillomatous lesions may develop as a result ofpronounced local proliferation. Such lesions areby no means unique and similar patterns may befound when other parts of the gastrointestinaltract are affected by lymphoma. 5Although difficult, an early diagnosis of

primary oesophageal lymphoma seems to be vitalas the response to treatment is often good.Table 2 shows that this is well documented forHodgkin's disease. Four of the six patientssurvived five years; two of these four patientswere still alive beyond that period, including ourcase 2 patient, the only long term survivortreated exclusively with combination chemo-therapy.Of the three patients that died, the cause of

death was not mentioned in one case, a secondpatient died of oesophageal recurrence,8 thethird succumbed to systemic lymphoma fiveyears after irradiation of a single oesophagealmanifestation; local treatment had been com-pletely successful, as indicated at necropsy,which failed to reveal any signs of malignancy inthe oesophagus.4 With the few data presentlyavailable, it is difficult to assess whether isolatedprimary involvement by non-Hodgkin'slymphoma would be equally responsive to treat-ment; our case 1 patient died of complicationsbefore any relevant treatment could be under-taken, whereas follow up in the case reported byBerman et al'6 was too short; only successful localexcision of the tumour was reported although'radiotherapy and chemotherapy were recom-mended to the patient'.Long term survivors (six to nine years) after

irradiation or chemotherapy have been describedin patients in whom primary oesophageal non-Hodgkin's lymphoma was part of more wide-spread disease.'2 '5 We have little reason to

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998 Taal, Van Heerde, Somers

TABLE I Characteristics before treatment ofpatients (all men) with isolated malignant lymphoma ofthe oesophagus

Author Age Interval (y) Oesophageal Histology Presenting symptoms

Hodgkin's disease:Bichel4 21 1 Distal Unspecified Dysphagia, itchingHambly and Blundell' 41 11 Middle Nod scier DysphagiaStein et al'7 30 - Proximal Nod scler Dysphagia, odynophagiatAgha and Schnitzer3 28 1 1 Distal Unspecified Dysphagia, weight loss > 15 kgWodzinski et a12 43 10 Distal Mixed cell DysphagiaCase 2* 34 13 Middle Nod scler Dysphagia, weight loss >10 kg

Non-Hodgkin's lymphoma:Berman et al'6 48 - Distal Large cell Chest pain, weight loss >7 kgCase 1* 59 - Middle+distal Centrocytic Chest pain, fatigue, fever

*Present study; todynophagia induced by alcohol ingestion. Nod scler=nodular sclerosing Hodgkin's disease.

TABLE II Results oftreatment in patients with isolated malignant lymphoma ofthe oesophagus

Previous Treatment ofoesophageal SurvivalAuthor Age (y) treatment lymphoma (months)

Hodgkin's disease:Bichel4 21 RT Axl Ln RT+ 44 Gy 62Hambly and Blundell8 41 RT Med Ln RT 9Stein et al'7 30 - Local excision, RT 40 Gy >68Agha and Schnitzer3 28 RT Med Ln RT 22 Gy, CTt 60Wodzinski et a12 43 CTt Oesophagectomy, CTt > 12Case 2* 34 RT Med Ln CT§ >60

Non-Hodgkin's lymphoma:Berman et al l6 48 - Local excisionCase 1* 59 - None 1

*Present study; t3xMOPP (mitoxine, vincristine, procarbazine, prednisolone) and 3xMVPP(mitoxine, vinblastine, procarbazine, prednisolone); t 6xEVAP (etoposide, vinblastine,doxorubicin, prednisolone); §8 xMOPP; RT=radiotherapy; CT=chemotherapy; Axl=axillary;Ln=lymph nodes; Med=mediastinal.

assume that the response of solitary lesionswould be fundamentally different.

Given the rarity of isolated primary oeso-phageal involvement by lymphoma, one mayquestion its clinical significance. Nevertheless, itis our opinion that clinicians should be familiarwith its clinical picture as much is at stake; thediagnosis is easily missed, which may have farreaching consequences in terms of prognosis.

Dysphagia or, occasionally, more atypicalcomplaints related to the upper gastrointestinaltract developing in young patients with a historyof lymphoma warrants suspicion, even in theabsence of specific symptoms, enlarged lymphnodes, or a long disease free interval. Histo-logical proof may be difficult to obtain butshould be vigorously pursued.

Lacking sufficient data, specific advice abouttreatment cannot be given; both local andsystemic approaches have resulted in long termsurvival. Our findings suggest that MOPPcombination chemotherapy may be successfully

applied. It presents a useful alternative forpatients in whom a local approach is contra-indicated - for example, those with a history ofmediastinal irradiation, when more radiotherapyis not an option.

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2 Wodzinski MA, Gavalos M, Brown MJ, Thorpe JAC.Hodgkin's disease of the oesophagus. Acta Haematol 1988;79: 221-3.

3 Agha F, Schnitzer B. Esophageal involvement in lymphoma.Amj Gastroenterol 1985; 80: 412-6.

4 Bichel J. Hodgkin's disease of the esophagus. Acta Radiol1951; 35: 371-2.

5 West WO, Bouroncle BA. Spontaneous perforation of theesophagus in Hodgkin's disease. Am J Gastroenterol 1960;33: 335-42.

6 Surks MI, Guttman AB. Esophageal involvement inHodgkin's disease. Americanjournal Digestive Diseases 1966;11: 814-8.

7 Ehrlich AN, Stolder G, Geller W, Sherlock P. Gastrointestinalmanifestations of malignant lymphoma. Gastroenterology1968; 54: 1115-21.

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12 Nissan S, Bar-Moar JA, Levy E. Lymphosarcoma of theesophagus: a case report. Cancer 1974; 34: 1321-3.

13 Lambert A. Malignant tracheoesophageal istula secondary toHodgkin's disease. J Thorac Cardiovasc Surg 1975; 69:820-5.

14 Davis JA, Kantrowitz PA, Chandler HL, Schatzki SC.Reversible achalasia due to reticulumcell sarcoma. N EnglJMed 1975; 293: 130-2.

15 Carnovale RL, Goldstein HM, Zornoza J, Dodd GD.Radiologic manifestations of esophageal lymphoma.American Journal of Roentegenology, Radium Therapy andNuclearMedicine 1977; 128: 751-4.

16 Berman MD, Falchuk KR, Trey C, Gramm HF. Primaryhistocytic lymphoma of the esophagus. DigDigSci 1979; 24:883-6.

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18 Traube M, Waldron JA, McCallum RW. Systemic lymphomainitially presenting as an esophageal mass. Am JGastroenterol 1982; 77: 835-7.



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