Aeta path. microhiol. scandinav. 74, 487-494, 1968

The Department of Pathology, Bispehjerg Hospital, Copenhagen, Denmark. (Head : Charles Johansen).

PRIMARY SUPERFICIAL CARCINOMAS OF THE DUODENUM

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ELLA LAMEN and AAGE JOHANSEN Heceived 25.v.68

Our knowledge concerning early malignant changes in the small bowel is very restricted, since tumours in this localization often are first considered late in the differential diagnosis of gastro-intestinal neo- plasms. This is the case with the duodenum too and especially with carcinomas of the first part of it. In this region malignant tumours are exceedingly rare and since their symptoms are very like those displayed by diseases of the stomach or by duodenal ulcers, the diag- nosis is often first made, when the process is widespread.

It is the purpose of this paper to report two cases of initial malig- nancy in this the first part of the duodenum and to discuss the histo- genesis. Both cases are incidental findings in the duodenal edge of gastric ulcer-resection specimens. Since the very small carcinomas have hardly given any symptoms, only a h i e d survey of the clinical histo- ries will be given.

C A S E R E P O R T S Case 1

Male patient, born in 1884. Since 1926 he had suffered from pulmonary tuber- culosis. He had been treated with streptomycin and isoniazid. Lately he had de- veloped a fistula to the right axilla.

He had never had any dyspepsia until December 1964, when he was admitted to this hospital with haematemesis. Physical examination revealed an anaemic, mo- derately ill, old patient. The blood pressure was 100/60 mm Hg., the haemoglobin was 5.9 g/per cent. The sedimentation rate 13 mm/h. The bleeding continued and on January 25th 1965 a gastric resection according to the method Billroth I was performed (Dr. D. Andersen). The stomach was full of blood and a superficial ulcer with a bleeding artery was found. The duodenum was extraordinarily mobile and no infiltrations or ulcers could be palpated.

The postoperative run was dominated hy the senility of the patient. He died three weeks after the operation.

Pathological examination. The gastric resection specimen revealed, one cm distal to the proximal resectionborder, a small ulcer. The mucosa was moderately injected, but without other focal processes. At the distal part of the specimen a duodenal stump of about 2% cm was

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seen. This slump was macroscopically normal. No lymph nodes were found.

Microscopic examination revealed a small chronic ulcer situated in the top of the pyloric mucosa close to the small curvature. The fundic niucosa showed a moderately atrophic, chronic gastritis with severe reduction in the number of parietal cells. In the pyloric mucosa a severe gastritis with extensive intestinal metaplasia was found. No signs of malignancy were seen in relation to the ulcer or anywhere in the stomach.

The duodenal stump was available for study in four out of sixteen examined sections, At the first examination, the only finding was a moderate inflammation, but later at reexamination, the following oh- servations were made in one of the four sections: The proximal 7 mm distal to the duodenal-pyloric junction revealed nothing except a slight infiltration with lymphocytes and plasma cells in the lamina propria. More distally, the normal architecture of the mucosa was changed (Fig. 1). The villi had disappeared and the crypts had lost their perpen- dicular arrangement and instead composed a trabecular network of anastoniosing cords. The cells were atypical without regular polarity. The nuclei were enlarged, hyperchromatic and a great number of mitoses, including many tripolar and other atypical ones, were seen. Transitions between normal crypts and atypical cords were seen. Among the cords small clusters and also single tumour cells were sccn in the lamina propria. In the PAS-stained sections some of the tumour cells showed a slightly positive reaction. Nowhere did the malignant changes extend to the muscularis mucosae. In the most proximal part of the malignantly changed area the mucosa was thin and had begun to ulcerate.

In all sections from the duodenum, small areas with a PAS-positive gastric surface epithelium were seen intermingled with the duodenal cpi the1 ium.

The Brunner glands had nearly completely disappeared under the malignantly changed epithelium. About a centimeter of quite normal mucosa was seen distally. In this part, the Brunner glands reappeared and here small areas of metaplastic gastric epithelium were seen too. In all the sections, the serosa was normal.

Autopsy. A complete autopsy with microscopic examination was performed. Only pertinent observations will be described. The rest of the stomach was found to be normal. The duodenum was without the slightest sign of malignancy. The rest of the small bowel, the colon, the pancreas, the bile ducts, the liver and the lymph nodes were all with- out tumourformations. Very severe tuberculous changes were found in the right lung and the right pleura. These together with severe ate- lectases were considered the cause of death. The cerebrum was normal, considering the age of the patient.

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Summary. A 79-year-old man, born in 1884. Since 1926 a diagnosis of pulmonary tuberculosis had been established. After a few weeks with epigastric pains, the patient developed severe gastric bleeding and Billroth I resection was made. Three weeks later he died of pulmonary insufficiency. Pathological examination of the gastric resection speci- mens revealed an ulcer situated between the pyloric and fundic mucosa. No malignant changes were found in the stomach. At microscopic exa- mination of the duodenal stump at the distal part of the resection speci- men, a superficial carcinoma without any invasion of the muscularis mucosa was found 7 mm distal to the pylorus.

The autopsy revealed no other malignant lesions.

Case 2 This patient was a woman, born in 1901. In 1941 she developed lymphadenopathia

of the neck. According to her own informations, a malignant disease of uncertain nature had been diagnosed and she was given radiotherapy. The enlarged lymph nodes disappeared and she has never had similar symptoms.

In 1956 a cholecystectomy was performed. From about this time she suffered periodically from dyspepsia and in 1963 and 1964 she had dietetic treatment in another hospital. In February 1965 she was admitted to this hospital on accoant' of increasing pains in the epigastrium, vomitings and pyrosis. Physical examination revealed a woman in good health. The haemoglobin was 12.1 g/per cent. Sedimenta- tion rate 18 mm/per hour. An augmented histamine test showed 76 meq/l and 11.8 meq/hour. An X-ray of the stomach showed a prepyloric ulcer. On March 11th 1965, a Billroth I1 resection (Dr. Bach-Nielsen) was performed and a prepyloric ulcer was found. The duodenum was normal on inspection and nothing abnormal could be palpated. A frozen section of an enlarged lymph node in the ligamentum hepato- duodenale showed no sign of malignancy. The postoperative run was uncomplicated and the patient has been controlled in the out-patient department several times, latest May 1967, when she felt quite well.

Pathological examination. Macroscopic examination of the stomach revealed a small ulcer situated just above the pylorus. It measured 9 by 12 mm and was without any macroscopic signs of malignancy, The resl of the mucosa was normal. Distal to the ulcer, a duodenal stump, 2 to 3 cm long, was seen. It was without any pathological changes. No lymph nodes were found.

Microscopic examination revealed a classical prepyloric ulcer on the small curvature. At the distal border of the ulcer, the very beginning of the duodenal mucosa was seen. A moderately severe gastritis with a slight intestinal metaplasia was found in the pyloric part of the speci- men. In the fundic part of the specimen, a superficial chronic gastritis was seen. No sign of malignancy was disclosed in relation to the ulcer or anywhere else in the stomach.

The duodenal stump could be studied in four sections. In one of the sections (Fig. 21, about half a centimeter above the distal resection- border, the following observations were made: In the PAS-stained sec- tion a collection of very heavily PAS-positive cells were found in an extraordinarily large villlus and also affecting the two neighbouring ones. These cells were strongly Alcian blue-positive too, In the haema-

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Pig. 2. Case 2. A : The whole extension of the carcinoma is illustrated. (H&E X 110). B: Section showing the signetring cells. (H&E X 420). C : The relation of the car- cinoma to the Brunner glands. (PAS X 20) . D : The strong Alcian blue reaction of

the tumourcells. (Alcian hlue X 40).

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toxylin-rosin-stained section it was seen that the cells in the mosl luminal part had the appearance of typical signelring cells. At deeper sites the cells were more anaplastic and contained only small drops of mucous. A few atypical mitosis were seen. The atypical cells invaded the st roma between the crypt’s of Lieberkuhn, but there was no inva- sion of the Brunner gland layer and of the indistinct muscularis mucosa. The surface epithelium covering the atypical cells showed sonic irregular nuclei and had lost the goblet cells. The very first centimeter of the duodenum showed no pathological changes and neither did thc centimeter nearest to the resectionborder. The Brunner glands were normal in all parts.

Small areas of metaplastic gastric surface epithelium were seen in this and the other sections from the duodenum. Apparently they had no relatiori to the malignant area. The serosa was normal.

Suinniary. A 64-year old woman, born in 1901. According to her own information she had been treated for a malignant lymphadenopa thia of the neck in 1941. This information could not be verified. Since 1956 she had experienced periods with gastric pains of ulcertype. After having received dietetic treatment several times, a Billroth I1 resection was performed in April 1965. The operation and postoperative run were uncomplicated. Three and a half years later she was doing well. Pathological examination of the gastric specimen revealed a prepyloric ulcer. No malignancy was found in the stomach. Microscopical exami- nation of the duodenal stump disclosed a small superficial signetring cell carcinoma without any invasion of the muscularis mucosa.

D I S C U S S I 0 N

Adenocarcinoma is by far the most common type of malignant neo- plasms in the duodenum (Machella 1964). In case 1 the changes un- doubtedly illustrate the beginning of an adenocarcinoma. The malig- nant changes in the crypt’s of Lieberkuhn and transitions from normal to atypical epithelium were seen in many places. The anastomosing cords and the presence of single tumour cells situated outside these cords indicated invasion of the lamina propria. Since no invasion of the muscularis mucosae had taken place, the correct designation of the changes, according to the similar conditions in the stomach, might be: superficial or surface carcinoma of the duodenum. The same desig- nation could be used in case 2. Also here was an invasion of the lamina propria, since the anaplastic signetring cells were disorderly arranged. Neither in this case was any invasion of the deeper part of the mucosae. Since nothing of the specimens were left, the exact size of the surface carcinomas could not be determined in either of the cases. The malignant changes were found in only one out of four sections from the duodenal stump, indicating their very limited size. Both

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carcinomas had a slriking reseniblance to the superficial carcinomas of the stomach described by Konjetzny (1940) , Morson (1955) , Kuhlcn- cordt (1959) and others. Since lhcse two cases in fact arc localized to the howel mucosae, the phenomenon may be a positive contribulion to thc discussion concerning the precancerous role of intestinal nicla- plasia in the stomach.

On lhe other hand, i t was interesting to note a certain “gastrifica- lion” of the duodenal cpilheliuni in both cases. In case 1, corresponding to the malignant area, all Lhc villi and nearly all the Brunner glands had disappeared and small areas of gaslric epithelium were seen in all sections from the duodenum. The gastric epithelium was also seen in thc duodenal seclions from case 2. How often such metaplastic gastric cpithelium is found in the duodenum is the subject of an as yet not finished investigation. It is not a rare phcnornenon. It is not likely that the metaplastic epithelium has played an important role in the hislo- genesis of thc two carcinomas, but such melaplasia may have intcn- sified their similarity with the gastric superficial carcinomas. The possibility that the two carcinomas were not primary tumours can be left out of consideration. The location in the most luminal part of the in teslinal wall is a strong argument for this contention. Furthermore the gastric specimens were part of a material investigated for early gastric cancer. Both ulcers were conipletcly sectioned and a lotal of sixteen seclions from each specimcns were examined but any signs of malignancy were not disclosed. Besides the stomach carcinomas, the malignant tumours of the pancreas are often seen to invade the first par1 of thc duodenum. In case 1 the autopsy revealed a normal pan- creas and the history of case 2 precludes, nearly with certainty, a pan- creatic carcinoma.

To our knowledge, such superficial carcinomas of the first part of the duodenum have never been reported. All authors (e .g. Dixon et al. 1946, Machella 1961, U’ieners 1966) agree that carcinomas in this posi- tion are extraordinarily rare, Early, but more extensive carcinomas in relation to duodenal ulcers have been reported (Jefferson 1916, Dixon et al. 1946). It has been menlioned, that malignant changes may take place in the Brunner glands and precancerous lesions have been re- ported by Robertson (1941 ) . Early malignant transformations of hc- lcrotopic pancreatic tissue in this region (Duff , Foster & Bryan 1943) as well as in the stomach (Jarvi & LaurCn 1964) have been described, hul also these carcinomas havc been more widespread.

Some authors look upon the benign duodenal polyp as a precanccr- oils Icsion. According to Wieners (1966), the adenomatous polyps are most common in the supraampullary part of the duodenum. Malig- nant changes in such polyps have been reported by Ebert et al. (1953) and by Schiavi & L’olfn (1964) .

Although in this matter the starting point of duodenal carcinonias may be different, most authors agree with the point of view that the

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bulk of the lesions represent malignant changes in the duodenal mucosae itself as illustrated in the two reported cases.

S U M M A R Y

Two cases of primary superficial carcinomas of the first part of thc duodenum are reported. They were incidental findings in the duodenal edge of gastric resection specimens. The one illustrated the beginning of an adenocarcinoma, the other the beginning of a diffuse signetring cell carcinoma. Both had a striking resemblance to superficial carci- nomas of the stomach. In the mucosae of the two duodenal stumps “metaplastic” gastric epithelium were found. The possible role of this in the histogenesis of the tumours is discussed. Other early malignant changes in the duodenum are briefly mentioned.

R E F E R E N C E S

Dixon, C. F., Lichfman, A . L., Weber, H . M . h McDonald, J . R.: Malignant lesions of the duodenum. Surg. Gynec. Obstet. 83: 83-93,1946.

Duff, G. L., Foster, H . L. & Bruan, W . W . : Primary carcinoma of the infra-ampullary portion of the duodenum. With example of probable origin from aberrant pan- creatic tissue. Arch. Surg. 46: 494-503,1943.

Jefferson, G.: Carcinoma of suprapapillary duodenum casually associated with prc- existing simpel ulcer. Britt. J. Surg. 4: 209-215,1916.

Jarui, 0. & LaurCn, P.: Gastric glandular tumours provided with excretory ducts and criticism of the theory of the tumours arising in heterotopic pancreas. Obser- vation on the occurrence of atypical glands in the stomach. Acta path. micro- bial. scandinav. 62: 1-23,1964.

KonjefznIl, G. E . : Der oberfliichlichc Sleimhaut Krebs des Magens. (Ein weitere Bei- trag znr Kenntnis des Magenkrebses im Beginn). Der Chirurg. f2: 192-202,1940.

Kuhlencordt, F.: Das carcinoma in situ des Magens und der kleine Magenltrehs, Katamnestische Untersuchungen von 42 Fallen. Dtsch. med. Wschr. 84 : 2111- 2115,1959.

Machella, T. E.: Tumours of the small intestine. In Bochus: Gastroenterology vol. 11. 2. edit. W. B. Saunders Company, Philadelphia and London 1964.

Morson, B. C.: Carcinomas arising from areas of intestinal metaplasia in the gastric mucosae. Brit. J. Cancer 9: 377-385,1955.

Robertson, H . E.: The pathology of Brunner’s glands. Arch. path. 31 : 112-130,1941. Schiaui, G. F. & Volta, A . : Considerazioni radiologiche su 6 Casi di Adenocarcinoma

primitivo del Bulho e della Porzionc sovra-ampollare del duodeno. Arch. ital. Mal. Appar. 31: 193-216,1964.

Wieners, H . : Seltene gutartige und bosartige Wandverlnderungen des Duodenum. Der Radiologe. 6 : 372-380,1966.