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CANCER CLINICS Cyrus E. Rubin CA Cancer J Clin 1956;6;136-140 DOI: 10.3322/canjclin.6.4.136

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seen to be distorted (Fig. 1, A).. The barium examination was interpreted as a large nodular carcinoma extending from the fundus toward the prepyloric antrum (Fig. 1, B). in retrospect, the roentgenograms a year previously sug gested similar but less marked neoplastic involvement. Gastroscopy was deemed in advisable since the esophagogastric junc tion was involved by tumor. On the basis of the gastric cytological diagnosis, surgerywas advised. At Iapa rotomy the liver and pelvis were free of tumor. The mass that had been felt on rectal and pelvic examination was a calci fied fibroid within an atrophic uterus. The tumor seemed restricted to the stomach. It was a bulky mass that extended from the cardiac end nearly to the pylorus. It felt rubbery and small extensions into adjacent lymph nodes seemed to he pres ent. A total gastrectomy, esophagojejunos t()my, and jejunojejunostomy were done. Roentgen-ray therapy was started eight days after operation; a total depth dose of 2000 r was administered to the upper abdomen over a sixteen-day period. Both three and ten months postoperatively the patient required hospitalization for epi sodes of intestinal obstruction. They sub sided promptly after alimentation and in tubation. Initially the patient barely main tained her body weight and did poorly. A right upper-quadrant mass in the region of the liver became apparent. Only small meals were possible and frequent, foul, fatty stools were a problem. A year post operatively she gradually tolerated more food and the diarrhea subsided. With her improvement in nutrition the right upper quadrant mass disappeared. A year and a half after operation the patient had re gained most of her previous body weight, was feeling fine, and doing most of her own housework. At the celebration of her golden wedding anniversary her friends were pleased to see her eat as large a meal as the other guests. Discussion
DR. CYRUS E. RUBIN: When first ob

hopelessly advanced gastric carcinoma, with metastases evident in the pouch of Douglas. Nevertheless, there were certain clinical findings that suggested that her prognosis was not necessarily a poor one. The very size of the mass and the rela tively long duration of the illness was evi dence of the patient's ability to resist her tumor. Furthermore, complete diagnostic work-up by modern techniques produced information that prompted surgical inter vention followed by roentgen-ray therapy. The wisdom of this course of action was borne out by the subsequent course. A year and a half after treatment she was back in her home, living an almost normal life. This offered a marked contrast to her miserable preoperative condition. At the worst, she was an example o excellent palliation and atthe best, she represented a cure. 1 wonder if I could have a descrip tion of the preoperative cytological exam ination of the stomach? Cytology. CYTOLOGIST: After careful preparation to ensure an empty stomach free of food and detritus, exfoliated gas tric cells were collected by the method of chymotrypsin lavage.5 This technique gives no more discomfort than the usual gastric analysis. Chymotrypsin is a safe enzyme that liquefies the mucous barrier covering the gastric mucosa and releases freshly exfoliated cells that are embedded in thismucous layer. The smears were quite cellular. Occa sional groups of normal gastric columnar cells were seen; however, the predominant cell type was lymphoid. The cells were

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served, the patient

presented

a picture of

FIGURE

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FIGURE 2. Lymphoma cells. (X 300.)

rather uniform in appearance and only slightly larger than the normal columnar cells. There was not the definite increase and variation in nuclear size so typical of carcinoma. The cells occurred singly rather than in clumps. Because of this uni formity in size and relative lack of nuclear enlargement, the diagnosis was almost missed with the usual low-power scanning lens (X 100). Upon shifting to the high dry objective (X430) it became apparent to the scanner that numerous cells that had been ignored were actually malignant. The lymphoid nuclei exhibited rare mi totic figures, closely packed chromatin aggregates, scant karyoplasm, and nucleoli that were less prominent than those of carcinoma. Occasional primitive reticu lum cells had more vesicular nuclei. The cytoplasm was usually sparse, forming a thin rim about the nucleus; at times it was scarcely discernable. Because of these morphological findings, the preoperative cytological diagnosis was malignant lym phoma of the stomach. The cellular find ings are illustrated in Fig. 2.
DR. RuBIN: Thank you. I am willing to

and may be misinterpreted as normal, benign gastric ulcer or carcinoma. Occa sional radiological diagnoses have been made, but they usually represent clever deductions arrived at from a knowledge of the total clinical situation. Correct gastroscopic diagnoses are infrequent. The usual visual interpretation is carcinoma. Itisnotsurprising thattheradiologist and gastroscopist have difficulty, since the sur geon at laparotomy is often unable to de termine the true nature of the lesion as he holds it in his hand. The pathologist may he equally hard pressed to make thegross diagnosis. It is, however, frequently pos sible to make a definitive diagnosis of ma lignant lymphoma of the stomach by ex foliative cytology. Gastric lymphomas are thought by most students to comprise less than 2 per cent o all tumors of the stomach. From these figures, it would seem that such a diagnosis is of little practical importance. Actually, this is far from the truth because the gastric lymphomas comprise an inor dinately large percentage of the five-year curesof allgastric cancers. Furthermore, they differ from carcinoma of mucosal origin in their tendency to remain local ized, to respond to radiation, and to have

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a better prognosis. Itistragic to allow

such patients to go to their deaths with no attempt at treatment because of a mis taken clinical diagnosis of hopeless carci noma. There are many reports in the literature of gastric malignant lymphoma cured by radiation or surgery alone or in combination. A trial of therapy by a rela tively small lymphocidal dose of roentgen rays isalways justified. Even latein the course of the disease it should be at tempted, for there is reason to believe that the long duration of a malignant process may indicate a better prognosis. Repeated roentgen-ray therapy is feasible and war ranted for recurrences of residual tumor.

accept this cytological diagnosis and be lieve that it accounts for the clinical

course ofthepatient.
Discussion continued. Before we recog nized the typical morphology of gastric malignant lymphoma.' there was no definitive method of diagnosing these le sions short of histological examination. In this disease the clinical story is in no way typical. The roentgenograms are variable

Itmay producesurprising palliation and

long survival.

The patient's difficulties in her first

postoperative year merit comment. When patients have been subjected to total gas trectomy and upper abdominal radiation. itis not unusual for theirconditionto

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worsen before it improves. The patient's enlarging liver was interpreted as evidence of metastatic disease. Subsequent events proved this to be a nutritional effect upon the liver. I wonder if my colleague would comment on this aspect of the case.

ductionof a largequantity of hypertonic food into contact with the intestinal ab sorptive surface. This is the result of the loss of the controlling pyloric gate.

DR. RUBIN: Thank you.The manage

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ment of dumping and other effects of total DR. WADE VOLWILER: The necessitygastrectomy can be very trying to patient for total gastrectomy in a situation of this and physician alike. Persistence attimesis type leaves in its wake two profoundly rewarded by definite ameliorationof difficult gastrointestinal disturbances: mal symptoms. Some patients are permanently absorption of many nutritional elements crippled, whereas many improve within and dumping. A specific absorptive de the first postoperative year. Strict limita fect, which is invariably present, is an al tion of fluids during mealtime and fre most complete inability to absorb vitamin quent small feedings low in carbohydrate B12 owing to the absence of gastric in and high in fat and protein may prove trinsic factor. Without specific replace helpful. Empirically, it has become ap ment therapy, all of these patients will parent that highly concentrated foods, eventually develop pernicious anemia. such as rich desserts, are poorly tolerated. This inevitable sequel of total gastrectomy This is probably related to their high con is not obvious clinically owing to the fact centration of soluble carbohydrates, which that the normal liver's storage depot of promotes a rapid shift of fluid from the vitamin B,2 requires months to years to intravascular space into the gut lumen as become depleted. Moreover, many pa these substances go into solution. Potent tients receive polyvitamin injections, anticholinergic drugs and calcium car which protect them. It is unfortunately bonate may be employed symptomatically true that most of these patients do not sur for their constipating effect. Calcium salts, vive long enough for severe pernicious vitamin B,2, folic acid, iron, and fat anemia to become full blown and obvious. soluble vitamins should be given orally or The malabsorption defect of small in parenterally as needed to overcome the testinal function is far broader, however, effects of malabsorption. As Dr. Volwiler and really involves virtually all nutritional has told you, the most effective method of elements. Whereas steatorrhea is most maintaining the patient's nutrition remains prominent, severe nitrogen loss regularly hyperalimentation. If the uncomfortable accompanies it. The entire explanation for dumping symptoms can be minimized, the this is as yet unknown. Administration of patient usually can compensate by over eating. supplements of oral bile salts, pancreatin, tween 80, and pre-emulsified fat singly or I wonder whether my colleague from in combination has not improved absorp the Pathology Department would like to comment anddescribe this patient's lesion. tion in this type of patient. The main therapeutic approach is plain overeating to guarantee adequate daily absorption. Pathology

In many such patients, the major limit

ing factor in nutrition is the early dump ing syndrome, which makes eating a formidable and fearsome event. This puzzling annoyance involving widespread production of both gastrointestinal and cardiovascular symptoms has recently been much clarified by work done at Me morial Hospital by Henry T. Randall's group who have beautifully demonstrated a marked shift of the plasma fluid to the upper small bowel after the rapid intro

DR.

IRVING SCHULDBERG:

Tumors

of

the malignant-lymphoma series are gen erally grouped into the following common varieties: lymphosarcoma, reticulum-cell sarcoma, Hodgkin's disease, and follicular lymphoma. Of the malignant lymphomas of the stomach, lymphosarcomas and reticulum-cell sarcomas are relatively

common, whereasHodgkin's disease and

follicular lymphoma a rigid classification are rare. In actuality is impractical, as the

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histological pattern of most malignant lymphomas is not static. Two or more his tological types may coexist in the same tu mor at the same or different times. Thus it is best to consider malignant lymphomas as a single neoplastic entity, which may be multiform morphologically. The distinction between malignant lym phomas and anaplastic carcinomas may

pose a difficult problem. In an individual

case such criteria as the relation of tumor

were kidney-shaped and contained a prominent nucleolus. In some areas, cells resembling lymphoblasts merged imper ceptibly through transitional forms to readily recognizable reticulum cells. The proximal and distal lines of resection of the stomach were free of cancer as were the lymph nodes. My final diagnosis was malignant lymphoma of the stomach, with surgical margins and lymph nodes clear.

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to normal epithelium, the preservation or

destruction of the muscularis mucosa, the presence or absence of tumor acini or columns, and the production of mucin may be crucial differential points. One may still have to depend on the ultimate biological course of the tumor and its radiosensitivity to make the diagnosis. Nevertheless, in some cases, uncertainty as to the primary cell type will remain. Returning to the case under discussion, the surgical specimen submitted was a total stomach and attached omentum. The proximal two thirds of the stomach contained an ulcerated, foul-smelling, partly necrotic, fleshy mass protruding ap proximately 2.5 cm. into the lumen. The muscularis externa appeared normal grossly. The mass was sharply delineated peripherally by a sessile ridge. Eight non descript lymph nodes were found in the attached omental tissues. Microscopic ex amination revealed a highly cellular tumor involving the mucosa and submucosa. The mucosal surface was partially ulcerated. Where it was preserved, the distinction between tumor cells and residual mucosal glands was distinct. The neoplastic ele ments resembled reticulum cells. The cell cytoplasm was sparse and many nuclei
1. Cooper, W. A., and Papanicolaou, G. N.: Bal loon technique in the cytological diagnosis of gastric cancer. J.A.M.A. 151: 10-14, 1953. 2. Graham, R. M.: Cytologic diagnosis of gastric cancer. [Ahstr.] Proceedings of the Symposia on Ex foliative Cytology; Cancer Detection and Diagnosis. Atlanta, Georgia. Medical College of Georgia. 1953: pp. 38-39. 3. Klayman, M. I.: Kirsner, J. B., and Palmner, W. L.: Gastric mm;aligi;ant lym;;phomna: increasing ac curacy in diagnosis. Gastroenterology 29: 536-547; disc. 548. 1955. 4. Rubin, C. E.: Newer advances in the exfoliative cytology of the gastrointestinal tract. Ann. New York Acad. Sd. 63: 1377-1398, 1956.

Conclusion Da. RUBIN: Thank you. In conclusion

1 would like to emphasize the positive as pects of this depressing problem of gastric malignant tumors. We have presented a rare but relatively hopeful type of gastric cancer. Admittedly our cure rate for the usual type of adenocarcinoma is very low despite continued improvement of sur gical therapy. By early accurate diagnoses the physician may avail himself more completely of the benefits of currently available surgical techniques. Selective screening of certain asymptomatic can cer-prone patients is desirable, for it will detect some curable disease. These ap proaches will undoubtedly increase our cure rate, but unfortunately many will continue to die despite our efforts. In order to maintain a proper perspective, one must try to remember that statistics do not matter to the cured patients; for them, it is 100 per cent. One must use the best methods available until more defini tive preventive, palliative, and curative measures are developed. They are being eagerly sought and probably will be found when we have more knowledge regarding the pathogenesis of human gastric cancer.
5. Rubin, C. E., and Benditt, F. P.: A simplified technique using chsm;;otrypsin lavage for tue cytologi cal diagnosis of gastric cam;cer. Cancer 8: 1137-1141,

References

1955.
6. Rubim;, C. E., and Massey, B. W.: T/;e preopera tive diagnosis of gastric and duodenal ,naligr;ant lymm;phoma by exfoliative cytology. Cancer 7: 271-288, 1954. 7. Rubin, C. E.; Massey, B. W.; Kirsner, J. B.; Paln;er, W. L., amid Stom;ecyp/;er, D. D.: T/;e clim;ical value of gastroim;testinal cytologic diagmiosis. Gastro em;terology 25: 119-138; disc. 153-155, 1953. 8. Traut, H. F.; Rosent/;al, 81.; Harrison, J. T.; Farber, 5. 51., and Gri,,ies. 0. F.: Eval;satiom; of cytologic diagnosis of gastric camicer. Surg., Gym;ec.

& Obst. 95: 709-716, 1952.

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