Gut 1993; 34:994-998 CASE REPORTS Isolated primary oesophageal involvement by lymphoma: 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 Cancer Institute, Department of Medical Oncology, Amsterdam, The Netherlands B G Taal P Van Heerde R Somers Correspondence to: B G Taal, MD, The Netherlands Cancer Institute, Department of Medical Oncology, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands. Accepted for publication 11 November 1992 Abstract Primary oesophageal involvement by lymph- oma in two patients, one with Hodgkin's disease and one with non-Hodgkin's lymph- oma is reported. In both, there were no manifestations of the disease outside the oesophagus, which is exceptionaily rare. In the patient with non-Hodgkin's lymphoma, the oesophageal tumour was the first manifesta- tion of lymphoma. Shortly after admission he developed a tracheo-oesophageal fistula from which he died before treatment could be started. In the patient with Hodgkin's disease, isolated oesophageal lymphoma was the first relapse after a 13 year interval free of disease. As he had previously received mediastinal irradiation he was treated with combination chemotherapy that resulted in long term survival (>five years). Several other long term survivors have been described but only after radiotherapy or surgery. These findings suggest that systemic chemotherapy may be equally successful in treating isolated primary oesophageal lymphoma, thus offering an alternative for those patients in whom local treatment is contraindicated. (Gut 1993; 34: 994-998) Lymphomatous involvement of the oe wall is rare. According to published st Figure 1: Case I (non-Hodgkin's lymphoma): barium swallow at presentation (A a showing irregular narrowing and ulceration of the oesophagus; shortly aftervards a oesophagealfistula developed (C). mainly associated with Hodgkin's disease, where it has been reported in up to 6% of cases in postmortem studies; the incidence of oesophageal invasion by non-Hodgkin's lymphoma does not exceed 1-6%.'2 Since 1935, only 90 cases of oesophageal lymphoma (53 Hodgkin's disease, 37 non-Hodgkin's lymphoma) have been des- cribed worldwide. 1-18 In most patients, secondary involvement as a result of enlarged mediastinal lymph nodes was either shown or implied. Primary involvement, however, defined as lymphoma developing in the oesophageal wall itself, seems to be exceptionally rare, especially in its isolated form: we have been able to identify only six cases in which patients presented with oesophageal tumour as the only manifestation of lymphoma (five Hodgkin's disease, one non-Hodgkin's lymphoma).? 48 1617 In this report we present two other patients from The Netherlands Cancer Institute with isolated primary oesophageal involvement by lymphoma. Their case histories show the diag- nostic problems that may be associated with this disease. Case 1 In September 1976 a 59 year old man was admitted to a local hospital for evaluation of sophageal intermittent complaints of retrosternal pain adies, it is related to the ingestion of food, but sometimes also occurring at night. Barium swallow showed an irregular mucosal pattern in the midoeso- phagus. Endoscopy disclosed abnormal mucosa at 26 cm from the incisors; biopsies showed chronic inflammation. While being evaluated for dysphagia he developed symptoms of intestinal obstruction with severe vomiting, caused by a large tumour in the sigmoid colon. A negative metastatic survey was followed by resection. Pathological examination showed a Dukes's C adenocar- cinoma. The patient made an excellent recovery from this operation. Apart from relief of intes- tinal obstruction he also experienced relief of dysphagia that supported the hypothesis that oesophagitis 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 from broncho- retrosternal pain and discomfort there were also complaints of fatigue, anorexia, and intermittent 994 t...: on May 7, 2022 by guest. Protected by copyright. http://gut.bmj.com/ Gut: first published as 10.1136/gut.34.7.994 on 1 July 1993. Downloaded from
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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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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
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.
,'o4 6 A 26O - B I .:........."..".~ -:.. Coa |b a] rI D IE "..I ~I
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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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.
1 Trotman BW, Glick JM, de Barros SGS, Atkinson BF.Dysphagia in a patient with Hodgkin's disease.JAMA 1980;244: 2552-3.
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.