382 BRIT. J. SURG., 1972, Vol. 59, No. 5, MAY

SQUAMOUS CARCINOMA OF THE STOMACH FOLLOWING CORROSIVE ACID BURNS

BY HENRY EATON* AND G. E. TENNEKOON DEPARTMENTS OF SURGERY AND PATHOLOGY, UNIVERSITY OF CEYLON, PERADENIYA, CEYLON

SUMMARY T w o cases of primary squamous-cell carcinoma

arising in a stomach damaged by corrosive acid burns are reported. Thirty-three previously reported cases of pure squamous carcinoma of the stomach are tabulated and their pathogenesis is discussed. A plea is made for treating corrosive acid burns of the stomach by some form of resection of the entire area involved rather than by more conservative methods, such as gastrojejunostomy, which have been used i n the past.

SQUAMOUS carcinoma of the stomach has rarely been reported in the literature. Dahlin (1956) failed to find a single case on reviewing 11,000 cases of carcinoma of the stomach seen at the Mayo Clinic between 1907 and 1955. Dreyer and Louw (1957) were able to collect only 9 cases from the world literature, to which they added I case of their own. Boswell and Helwig (1965) found reports in the literature of 43 cases of gastric carcinoma containing squamous tissue, but only 18 of these were pure squamous carcinomas, the rest being mixed squamous and mucin-secreting tumours (adeno-acanthomas). To the first group they added 12 cases of pure squamous carcinoma obtained from a study of 2634 cases of carcinoma of the stomach in the files of the Armed Forces Institute of Pathology. Only 3 further cases of pure squamous carcinoma of the stomach have subsequently been reported (Altshuler and Shaka, 1966; Urban, 1966; Sano, 1967- Table I ) . In all the reports there has been controversy about the possible origin of the turnours.

T h e cases reported here are unique in that in each instance the squamous carcinoma developed in a stomach which had been damaged by corrosive acid many years earlier.

CASE REPORTS Case I.-R. V., a Sinhalese male, aged 39 years,

presented at the General Hospital, Kandy, complaining of vomiting after meals and loss of weight of 3 months' duration. Both symptoms had been progressive from their onset, and at the time of admission (23 March, 1970) the patient was vomiting soon after nearly every solid meal. He had begun to vomit even liquids during the past 2 weeks. The vomitus had neither been blood-stained nor appeared to contain bile at any time.

At about the age of 12 the patient had become involved in a drinking bout and whilst under the influence of alcohol had drunk about one cupful of a liquid which he had later realized was an acid (this was probably acetic acid as it was freely available in the part of the country where he lived because of its use in the manufacture of

* Present address and address for reprints: 17 Ritchie Way, Cloverdale, West Australia 6105.

rubber). Soon afterwards he had begun to vomit rather severely and had been given a stomach wash. He had continued to vomit blood-stained material and had been treated with intravenous fluids as he had found difficulty

Table I.-CASES OF PURE SQUAMouS CARCINOMA OF THE STOMACH REPORTED IN THE LITERATURE -

CASE

- - I 2 3 4 5

6

7 8

9 I 0 I 1 I 2 I3 14 15 16 I7

IS I9 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35

__

AUTHOR

(1936)

(1940)

Weil (1936) Gauthier-Villars and Leger

Scheffler and Falk (1940) Reich (1944) Puccini and Stigliani (1950) Diaz (1951) Hicks (1953) Lawe (1955) Lange (1955) Dreyer and Louw (1957) Cruze, Maas, Clarke, and

Johnston and Pitts (1962) Boswell and Helwig (1965) Boswell and Helwjg (1965) Boswell and Helwig (1965) BosweU and Helwig (1965) Boswell and Helwig (1965) Boswell and Helwig (1965) Boswell and Helwig (1965) Boswell and Helwig (1965) Boswell and Helwig (1965) Boswell and Helwjg (1965) Boswell and Helwig (1965) Boswell and Helwig (1965) Altshuler and Shaka (1966) Urban (1966) Sano (1967) Eaton and Tennekmn (1972) Eaton and Tennekoon (1972)

El-Ferra (1960)

- AGE AND SEX

.__ - -- - M .

54 F. 41 M.

57 M.

47 M.

49 M.

58 M. 73 M. 65 F. 78 M. 56 M. 44 F. 52 M.

81 M. 36 M. 40 M. 52 M. 56 M.

62 M. 66 M. 66 M. 67 M.

71 F. 79 M. 75 M.

39 M.

--

68 M.

62 M.

57 F.

70 M.

-- -- 26 F.

SITE

Lesser curvature Fundus

Pylorus Pylorus

Lesser curvature

Pylorus Pylorus

Body Pylorus

Pylorus

-

- - - - Pylorus Cardia

7 in the pylorus, 4 in, the fundus,

' multiple tumours in I case

Body and cardia - - Body Body and cardia

in swallowing. He had made a slow recovery and had been discharged some 3 months later, at which time he had been able to take semisolid food. During the course of the following year he had returned to a normal diet of rice and curry but he had only been able to manage small quantities at a time, so that he had been forced to have meals every z hours in order to satisfy his hunger. Any attempt at ingesting a normal-sized meal had given rise to severe abdominal discomfort and vomiting.

The patient was found to be dehydrated and thin, weighing only 33.6 kg. The cardiovascular and respiratory systems were clinically normal, and physical examination revealed no abnormal findings in the abdomen or else- where.

On 4 April a barium-meal screening was carried out. The appearances were reported as those of 'a carcinoma of the body of the stomach, since a constant-filling defect was seen in this area. The stomach was greatly reduce: in size and the pylorus lay well to the left of the midline (Fig. I),

EATON AND TENNEKOON: SQUAMOUS CARCINOMA OF STOMACH 383

Gastric secretions collected overnight for 12 hours and !esser curvature just distal to the oesophagogastric were found to contain no free hydrochloric acid, and junction. The diseased area of the stomach was mobile gastric washings which were examined for malignant cells and metastases appeared to be confined to the few small showed a large number of squames with the cells appearing and hard lymph-nodes along the right gastro-epiploic uniform and the changes being of only Grade I intensity. vessels.

OrERATION.-on I 8 April, following adequate prepa- A near-total radical gastrectomy was carried out, the ration, the abdomen was opened through a midline tiny cuff of stomach at the cardiac end being anastomosed

to the apex of a loop of proximal jejunum which was brought up behind the colon. The limbs of the jejunal loop were anastomosed side to side to each other to form a gastric pouch.

pATHOLOGY.-The resected specimen was 123 cm. in length and consisted of almost the entire stomach distal to the cardiac orifice (Fig. 2). When opened along the lesser curvature, normal-looking gastric mucosa was seen at the pyloric end of the stomach, the mid-portion of the stomach was granular and devoid of normal epithelium, and apparently normal mucosa was seen again at the cardiac end (Fig. 3).

Histologically, the ulcerated area was a squamous carcinoma (Fig. 4), and sections taken from the edge of

FIG. case I . Barium-meal film showing the deformity in the body of the stomach together with shortening of the stomach which has drawn the duodenum to the left.

FIG. 2.-Case I . The resected portion of the stomach is shown with the clamp on the duodenal end.

FIG. 3.-Case I . The stomach has been opened along the lesser curvature to show normal mucosa towards the pylorus a grossly ulcerated portion of the stomach in the middle, and s m o h mucpsa towards the oesophageal end in the upper right-hand pornon.

epigastric incision. The first part of the duodenum was found lying across the midline with the pyloric part of the stomach well to the left. The antrum and the body of the stomach were markedly reduced in size and the peritoneal surface was smooth and shiny. This area was quite hard to the touch and the only area of the stomach which appeared normal was a 3.8-cm. segment of cardia, fundus,

FIG. 4.--Case I. Squamous carcinoma of the stomach ulcerated area. H. and 6. ( x So.)

from the

this area towards the cardia showed squamous epithelium all along it (Fig. 5) . Sections from the distal part of the ulcerated area near the pylorus showed a transition to gastric mucosa (Fig. 6). Serial sections showed that the whole of the stomach proximal to this transitional area was covered with squamous epithelium with no inter- vening islets of gastric mucosa. The muscle coat of the

384 BRIT. J. SURG., 1972, Vol. 59, No. 5, MAY

stomach showed diffuse fibrosis with breaks of a complete appetite had occurred and had become progressive, nature with scarring in the floor of the ulcer (Fig. 7). No causing a significant loss of weight. metastases were found in the lymph-nodes. Twelve years earlier the patient had accidentally

~OSTOPERATION.-The patient’s postoperative con- swallowed about a cupful of acid used for electroplating, valescence was complicated by a left subphrenic abscess after which she had vomited blood and subsequently had

FIG. S.-Case I. Photomicrograph showing the proximal part FIG. 6.-Case I . The junction of the squamous epithelium with the gastric mucosa at the distal part of the ulcerated area. of the stomach wall lined by hyperplastic squamous epithelium.

H. and E. ( x so.) H. and E. ( x so.)

FIG. 7.-Case I . Photomicrograph to show a break in the muscularis replaced by fibrous tissue. M, Muscle separated by fibrous tissue. H. and E. ( x 7 0 . )

which was drained on the seventeenth day after surgery. Following this there was rapid improvement and the patient was discharged home on 27 May, a little over I month after gastrectomy, having gained 4.5 kg. in weight and being able to eat a large plateful of rice without difficulty at a single meal.

The patient has been seen regularly at follow-up and has remained well. In April, 1971, his weight was stable at 44 kg. He has resumed work as a waiter, and has found that he can satisfy his hunger with about a cupful of rice (about half the quantity he was able to take soon after his operation), which is about the average quantity con- sumed at a single meal by a person not engaged in heavy manual work.

Case 2.-S. W. S., a Sinhalese housewife aged 26 years, was admitted to the Surgical Unit of the University at Kandy General Hospital on 7 Oct., 1970, complaining of progressive difficulty in swallowing of about 4 months’ duration. During this period the patient had also experi- enced pain in the upper abdomen radiating to the back which had been worse when she had been hungry. There had been no vomiting but regurgitation of food mixed with blood had occurred occasionally. The patient was able to swallow solids only if they were accompanied by a drink. Symptoms were worse on lying down and were relieved on sitting up. Over the past 4 months loss of

FIG. S.-Case 2 . Barium-meal film showing a normal oesophagus with a patulous oesoptiagogastric junction and a small part of thc stomach in the thorax.

developed difficulty in swallowing. One month later she had undergone an operation in the General Hospital, Colombo, where a sleeve resection of the middle of the body of the stomach had been carried out for an acid stricture. She had been discharged I month later free of symptoms, and had remained well until the present illness. In the intervening period she had married and had had I child.

Examination showed an anaemic and wasted woman who was in obvious pain and weighed only 23 kg. The abdomen was scaphoid and showed an old midline epigastric scar. Except for vague tenderness in the epi- gastrium, physical examination showed no abnormality in the abdomen or elsewhere.

EATON AND TENNEKOON : SQUAMOUS CARCINOMA OF STOMACH 385

Barium-meal screening carried out on 19 Oct. was oesophagus to be normal down to the level of the diaphragm from where a growth was found extending down to within 5 cm. of the pylorus (Fig. 11). The growth was closely adherent to the liver, diaphragm, and posterior abdominal wall structures.

reported as showing ‘the proximal seven-eighths of the oesophagus to be normal. The rest of the oesophagus appeared to have been resected. A small part of the stomach was in the thorax and there was a patulous

FIG. 10.-Case 2. Barium-meal film showing stomach at 24 hours.

a residue in the

FIG. 9.-Case 2. Barium-meal film showing the gross irregu- larity in the mid-portion of the stomach with normal mucosal folds in the distal few centimetres.

oesophagogastric junction (Fig. 8). There was gross irregularity of the mid-portion of the stomach with narrowing of the lumen (Fig. 9). There were two areas of severe stricture formation, as a result of which pockets had formed in the lesser curvature. The distal few centi- metres of the stomach showed normal mucosal folds, and the gastroduodenal junction was normal though stretched to some extent. At 24 hours there was a small residue of barium in the stomach (Fig. 10). The appearances were strongly suggestive of malignancy of the stomach, very probably superimposed on corrosion by acid. ’

On 17 Oct. the patient was oesophagoscoped and the oesophagus, though containing some fluid, was found to be clear up to 38 cm. Beyond this point the tip of the endoscope had to be deflected abruptly ( ? oesophago- gastric junction) and thereupon the mucosa appeared whitish, protuberant, and hard. A biopsy was taken from this area with some difficulty as the jaws of the instrument tended to slip off the mass.

The biopsy was reported as showing a squamous carcinoma.

OPERATION.-After adequate preparation, exploration was carried out on I Nov. employing a left-sided thoraco-abdominal incision through the bed of the seventh rib. A tumour about the size of a cricket ball was found in the upper part of the stomach and was densely adherent anteriorly to the left lobe of the liver and posteriorly to the structures of the abdominal wall, making resection impracticable. A palliative Roux-en-Y end-to-side oesophagojejunostomy was constructed at the level of the hilum of the left lung.

Postoperatively, the patient’s condition was unsatis- factory and she was managed in an intensive care unit; despite treatment she died on the morning of 3 Nov.

PATHOLOGY.-Only a partial post-mortem examination was allowed and the specimen removed showed the

FIG. 11.-Case 2. T h e stomach opened at the post-mortem examination to show the tumour extendine from the middle of the the

stomach to the oesophagogastric oesophagogastric junction.

- junction. T h e pointer is at

Histology showed a squamous carcinoma infiltrating the stomach widely and deeply.

DISCUSSION T h e pathological findings in Case I resemble

those reported by Watson, Flint, and Stewart (1936) in a case where the upper loculus of an hour-glass stomach-caused by stricturing from hyperplastic tuberculosis-was found to be completely lined by squamous epithelium except for a narrow area along the lesser curve of the stomach. T h e oesophago- gastric junction could not be identified from the mucosal aspect, suggesting that squamous epithelium

386 BRIT. J. SURG., 1972, Vol. 59, No. 5, MAY

had grown down from the oesophagus to cover the upper loculus.

In the present Case I the squamous epithelium found in the stomach was hyperplastic, was probably continuous with the epithelium of the oesophagus, and lined the whole of the stomach up to the distal margin of the ulcer. The fibrosis and discontinuity found in the muscularis subjacent to the squamous epithelium are evidence of the past damage to this area by the acid burns. In the cardiac portion of the stomach the gastric mucosa damaged by the acid had probably been completely replaced by epithelial downgrowth from the oesophageal mucosa, thus accounting for the achlorhydria found and the large number of squames seen in the gastric washings.

The malignant change that had subsequently occurred in the squamous epithelium had resulted in a pure primary squamous carcinoma.

In Case 2 there was also a past history of corrosive gastritis which had necessitated early surgery of an excisional nature. I t is reasonable to assume that the resection of the strictured area had removed only the worst-affected area, leaving behind damaged epi- thelium which had been replaced by squamous epithelium. The tumour that had developed sub- sequently had involved the stomach extensively and the oesophagus minimally. Though the pathological picture was not as clear cut as in the first case, it is reasonable to suppose that the malignancy had supervened on squamous epithelium which had replaced gastric mucosa damaged by acid in this case as well.

Several explanations have been put forward with respect to the origin of squamous epithelium in the stomach. It has been considered to arise from (I) primitive undifferentiated basal cells in the mucosa, (2) heterotopic islets of squamous epithelium, (3) squamous metaplasia of gastric epithelium or a similar change occurring in an adenocarcinoma, and (4) a semisquamous epithelial layer covering the gastric mucosa (Duran-Jorda, 1945).

Squamous-cell metaplasia of the gastric mucosal epithelium though denied by Dreyer and Louw (1957) has been reported in I case by Hermann (191 I), and a similar change has been produced experi- mentally in rats by Futterer (1904) and Saxen (1952). Boswell and Helwig (1965) have also reported squamous metaplasia-at the edge of a perforated gastric ulcer. The possibility must be accepted of subsequent development of squamous carcinoma in metaplastic gastric epithelium.

The explanation advanced by Duran- Jorda (1945) of a semisquamous epithelial layer covering the gastric mucosa was favoured by Diaz (1951) to explain the changes that he reported in his case, but Altshuler and Shaka (1966) discount this theory as they hold that electron microscopy has not shown the presence of this additional layer. On the contrary, they support the possibility of heterotopic squamous epithelium being the source of many such tumours, as islands of squamous epithelium are well known to occur, particularly near the cardia and along the lesser curve (McPeak and Warren, 1948).

In the cases reported here, in view of the past damage to the gastric mucosa, it is held that the squamous epithelial change was caused by regenerative downgrowth from the oesophagus. This conclusion

is supported by the continuity of the squamous epithelium on the damaged area with that of the oesophagus.

Boswell and Helwig (1965), in analysing their 12 cases, found half of them suitable for onlv Dalliative procedures because of widespread intralacdominal metastases. No case survived more than I year. These findings are in direct contrast to those of other authors who report absence of metastatic spread and forecast a reasonable prognosis. Our first case appears to fall into this category since there was no metastatic spread and the patient is in good health I year after surgery. He should have a better prognosis than if he had had an equivalent gastric adenocarcinoma.

The 2 cases reported here have a particular surgical significance in that malignant neoplasia followed on corrosive acid burns of the stomach. It has been the practice when dealing with acid burns of the stomach to consider them benign and to treat them by gastro- jejunostomy or pyloroplasty, leaving the burnt area in situ. Paul (195I), in discussing the treatment of corrosive strictures of the stomach, stated that there appeared to be a place for partial gastrectomy rather than gastrojejunostomy as the latter may be followed by stoma1 or jejunal ulceration in later years and also because the possibility of malignant change cannot be discounted. Despite this he treated the patients reported by him by gastrojejunostomy only, and this appears to have been the practice followed by other surgeons too. A more radical form of surgery as suggested by us has only been performed in those cases where diffuse fibrosis has followed the corrosive burn (Strange, Finneran, Schumacher, and Bowman, 1951).

From the experience gained from these 2 cases it would appear that partial or subtotaI gastrectomy rather than a conservative procedure should be adopted in patients presenting with corrosive strictures of the stomach, as they might otherwise develop a malignant lesion many years later in the deeply burnt area.

~

-REFERENCES ALTSHULER, J. H., and SHAKA, J. A. (1966), Cancer, N.Y.,

BORST, M. ( I ~ o z ) , Die Lehre von den Geschwulsten, vol. 2,

BOSWELL, J. T., and HELWIG, E. B. (1965), Cancer, N.Y.,

CALDERARA, A. (1910)~ Archs Path. Anat., 200, 181. CRUZE, K., MAAS, H. E., CLARKE, J. S., and EL-FERRA, S.

DAHLIN, D. C. (1956), personal communication quoted by

DIM, J. R. C. ( I ~ s I ) , Surgery, St Louis, 30, 554. DREYER, B., and Louw, J. H. (I957), Br. J . Surg., 44,

DURAN-JORDA, F. (I945), Acta med. scand., 123, 26. EPPINGER, A. (1899, Prag. med. Wschr., 20, 218. FUTTERER, G. (1904), J . Am. med. Ass., 43, 1129. GAUTHIER-VILLARS, P., and LEGER, L. (1940), Annls Anat.

HERMANN, A. (1911)~ Wien kEin. Wschr., 24, 168. HICKS, J. D. (1953),J. Path. Bact., 66, 570. TOHNSTON, G. C., and PITTS, H. H. (1962), Can. med.

19, 831.

p. 645. Weisbaden: Bergmann.

18, 181.

(1960), Gastroenterology, 39, 787.

DREYER and Louw (1957).

425.

path. mid.-chir., 16, 1065.

Ass. J., 86, 376. LANGE, W. G. (1955), Prensa mid. argent., 42, 241. MCPEAK, E., and WARREN, S. (1948)~ A m . J . Path., 24,

971.

JONES AND CRUMPLIN: EPITHELIOMA O F MALHERBE 387

DE MARTEL, T., OBERLING, C., and PERNET, J. (I930),

PAUL, M. A. (IggI), Lancet, 2, 1064. PENNA DE AZEVEDO, A., and VILLELA, E. (1936), Mems

PUCCINI, C., and STIGLIANI, R. (1950), Archo De Vecchi,

SANO, R. (1967),Jap. J . Cancer Clin., 13, 465. SAXEN, R. E. (I952),J. natn Cancer Inst., 13, 441. SCHEFFLER, M. M., and FALK, A. B. (1940), Am. J .

Cancer, 38, 359. STRANGE, D. C., FINNERAN, J. C., SHUMACHER, H. B.,

and BOWMAN, D. E. ( I ~ s I ) , Archs Surg., Chicago, 62,

Bull. Ass. f r . Etude Cancer, 19, 470.

Inst. Oswaldo Cruz, 31, 719.

IS . 7 T ? . ?CO. REI&~-H. (I944), Virchows Arch. path. Anat. Physiol., URBAN, A. (1966), Acta med. pol., Vars., 7 , 227.

WATSON, G. W., FLINT, E. R., and STEWART, M. J. (1936), 312, 616. RORIG, R. (1895), l‘rimares Cancroid des Magens. B r . J . Surg., 24, 333.

Wurzburg : Schemer. WEIL, G. H. (1936), Strasb. mkd., 96, 45.

CALCIFYING EPITHELIOMA OF MALHERBE BY S. M. JONES AND K. H. CRUMPLIN

PRINCESS MARGARET HOSPITAL, SWINDON

SUMMARY Experience with 34 cases of calcifying epithelioma

of Malherbe is analysed, and the frequency of mis- diagnosis is noted. The apparent dramatic rise in incidence over the past few years may be due to an increasing awareness of the existence of this benign tumour by both clinicians and pathologists. Evidence is cited to support the view that the lesion arises from the hair-forming cells of the dermis.

CALCIFYING epithelioma of Malherbe was first described in 1880 by Malherbe and Chenantais, who stated that it was an epithelioma arising from the sebaceous glands and that it frequently became calcified. Beck in 1933 first likened the appearance and differentiation of the ‘tumour’ cells to hair- matrix cells. This opinion has subsequently been confirmed by Forbis and Helwig (1961), who first coined the term ‘ pilomatrixoma ’, and by McGavron (1965), who further confirmed the hair-matrix-cell origin by electron microscopy and histochemistry.

CLINICAL MATERIAL The earlier cases in the present series were found

from the pathological diagnostic index of the Pathology Department of the Princess Margaret Hospital, Swindon. In recent months increasing awareness has led to cases being more frequently diagnosed clinically and subsequently confirmed by routine microscopy. Twelve cases were recorded between 1962 and 1967, while 22 presented between January, 1968, and January, 1970 (Table I).

INCIDENCE The total number of all skin tumours excised and

submitted for histological examination in the period from 1962 to 1970 at the Princess Margaret Hospital, Swindon, was 2151. Thus, the incidence of epi- thelioma of Malherbe was 1’4 per cent.

The lesion was found in all age-groups between 3 and 96 years, but half of the patients were less than 20 years of age. In I patient a lump had been noticed only z weeks before presentation, but the majority had had symptoms for some months, and a few for ‘many years’. I n this series more females than males were affected, the ratio being 1.4 : I.

Anatomical Distribution.-There was a pre- dilection for the head and neck as the commonest site, but the upper and lower limbs were also involved.

Table PRESENTATION OF CASES

1962 3 1963 2 1964 I 1965 2 1966 2 1967 2 1968 6 1969 15 January, 1970 I

Total 34

Year No. of Cases

-

Table ZZ.-THE PREOPERATIVE DIAGNOSIS Preoperative Diagnosis No. of Cases

No diagnosis made I2 Calcifying epithelioma of Malherbe 9 Sebaceous cyst 7 Tuberculous node 2 Histiocytoma 2 Neurofibroma I Inclusion dermoid I

Total 34 -

The frequent occurrence near the eye noted by other authors (Richardson, Pinzon, Fetterman, Musgrave, and Gaisford, 1965) was confirmed. Size variation in our series was between 0.3 and 5 cm. in diameter.

CLINICAL PRESENTATION The lesion appears as a firm, rounded, lobulated,

occasionally tender nodule attached to skin but not to deep structures (Fig. I); occasionally it may be pigmented. Calcification, if present, may be demon- strated by a plain radiograph, but this can also occur in cysts and other skin tumours. The diagnosis was correctly made in a quarter of the present series, the frequency of other diagnoses being shown in Table I I .

PATHOLOGICAL FEATURES The lesion is a firm or hard, encapsulated tumour,

with a chalky consistency when cut across. Micro- scopically, the appearance is characteristic (Fig. 2) : sheets or clusters of basophilic and ‘ ghost’ or ‘ shadow’ cells are randomly placed in a scanty stroma. Various other cell types are seen, some of which are degenerate,