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The beginnings of gastric cancer
THE BEGINNINGS OF GASTRIC JAMES
EWING,
CANCER*
M.D.
Director, The MemoriaI HospitaI NEW
A
YORK,
accurate knowIedge of the beginnings of gastric cancer wouId direct the search for the earIy curabIe stages of the disease, probabIy throw Iight on the causation, and expIain many of the cIinica1 pecuIiaritiks. The most important contribution on this subject is that of Ver.4, from Marchand’s Iaboratory, (Arbeit, p. Instit. Leipsig, 190% 5, I.) Among 10,000 autopsies Verst: encountered I 2 earIyg astric cancers, unsuspected during Iife. They were usuaIIy smaI1, 0.5 to 5 ems. in diameter, circumscribed, sIightIy eIevated, sometimes eroded, infected, infiItrated with Ieucocytes, and a11 were adenocarcinomas. In several cases there was genera1 atrophic or hyperpIastic gastritis, and a history of aIcohoIism. It is thus apparent that gastric cancer often begins as a IocaIized overgrowth affecting primariIy previousIy norma ceIIs which show atypical overnutrition and overgrowth, and that infection, erosion and uIceration may supervene very earIy. I have seen three such cases at autopsy which presented the above structure. Rather different was the condition in a remarkabIe case of which I have seen onIy one exampIe. The antra1 mucosa was the seat of a foca1 hyperpIastic gastritis affecting much of this region. The gIands were moderateIy enlarged and the Iining ceIIs hyperchromatic. At many points over this area there were erosions of sIightIy eIevated patches, and here the gIands were distinctIy atypica1, hyperplastic, and beginning to invade through the muscuIaris mucosae. This was an earIy superficia1 adenocarcinoma arising at muItipIe points over a rather wide area of hyperpIastic gastritis. If this condition had progressed, it wouId probabIy have resuIted in a Iarge region of superficia1 N
* Read at a RoundTabIqConference
oncancer
N.
Y.
erosion with gradua1 extension of the disease through a11 coats of the stomach. I suspect that this is the mode of origin of many of the superfica1 erosive carcinomas of the pyIoric antrum in which there is no IocaIized tumor or uIcer, but onIy diffuse erosion of the mucosa and infiItration of the submucosa. It is a nice question over which to ponder:-what can be the cause of such a pecuIiar atypica1 hyperpIastic gastritis? It is not the usua1 chronic hypertrophic form of gastritis, with greatIy enIarged gIands and increased stroma, but one which is highIy atypica1 from the first and runs rapidIy into cancer. It suggests the IocaI action of some strongIy cancerigenie irritant. I have seen the same type of hyperpIastic gIanduIar inff ammation in the rectum which was the seat of carcinoma. The early Iiterature on gastric cancer shows that the deveIopment of adenocarcinoma from muItipIe foci has frequentIy been observed, especiaIIy by WaIdeyer and by Hauser, usuaIIy fron rather we11 defined areas with fuI1 deveIoped but smaI1 adenocarcinomas, separated by norma mucosa. The case which I have described showed diffuse atypica1 changes over the entire affected region, without any norma mucosa. Both these processes, especiaIIy the Iatter, probably Iead in Iater stages to the wide superficia1 uIcerating adenocarcinomas occasionaIIy encountered. Some other ways are known in which superficia1 erosive carcinomas begin. There is a group of cases in which the superficial epitheIium and that of the ducts remains intact, but the tubuIar gIand fundi break up and the maIignant epitheIia1 ceIIs infiItrate wideIy over the mucosa. I have pictured two such cases in NeopIastic Diseases. The earIy resuIt is a superficial eroding carcinoma without tumor formation or excavation What the Iater stages
at the Fiftieth Anniversary 204
of the Memorial HospitaI, May
z5,Ig34.
NEW
SERIES VOL. XXX],
No.
z
Ewing-Gastric
may be I do not know. Hayem* has described the development of a diffuse scirrhus or fibrous carcinoma in a case of diffuse parenchymatous gastritis in which the peptic gIands seemed to break down and the granuIar acidophiIe peptic ceIIs spread through the stroma giving origin to the cancer. I have seen one early eroding cancer which recaIIed this description. From the morphoIogy of these earIy eroding superfica1 carcinomas one may draw certain concIusions of practica1 interest. When the superficia1 Iining ceIIs remain intact one can hardIy assume that the process resuIts from the action of superficial irritants. It must arise from factors affecting the tubuIar portions of the gIands excIusiveIy and be referred to some other much more subtle and probably intrinsic factors. Since a Iarge proportion of the gastric cancers are superficia1 and mereIy erosive in their earIy stages they wiII probabIy not be reveaIed to the radioIogist by any definite tumefaction or by any fiIIing defect, but must be found, if at aI1, by some other criterion. It may be suggested that these earIy criteria probabIy take the form of obhteration of the rugae or fixation of the mucosa. CongenitaI or acquired structura1 abnormaIities give rise to a smaII proportion of gastric cancers. Heterotopias of intestinal mucosa are frequentiy found in the pyIoric region and some authors have traced uIcers and cancers to this origin. Pancreatic isIands have been found in the stomach waI1 and these must be considered as rare sources of peculiar types of carcinoma. Misplaced isIands of gastric gIands may be found in the stomach waI1. RecentIy Pack discovered almost by accident, by a thorough, very minute inspection of x-ray plates taken by Dr. Hauser, and removed a smaI1 fulIy maIignant smaI1 ceI1 adenocarcinomatous noduIe deep in the submucosa of an otherwise norma stomach. Carcinoma arising in the ordinary type of chronic hypertrophic gastritis seems to be rare, aIthough Konjetzny frequentIy finds gIand heterotopia. In the poIypoid form of chronic gastritis singIe or muItipIe * Hayem, G. Rd. WC. anat. 1905, 80, 649.
Cancer
Beginnings
A me&m
Journal of Surgery
205
carcinomas are frequent, and the natura1 termination of this disease in the stomach, as in the colon, is death from cancer. SoIitary poIypoid adenomas and Iow grade adenocarcinomas give rise to the very characteristic buIky maIignant tumors of the stomach which give unexpectedIy good resuIts from resection. Their detection in the earIy stages is readiIy accompIished. These observations on earIy gastric cancer have a bearing on the subject of uIcero-cancer. It appears that adenocarcinomas tend to uIcerate at a very earIy stage. That they may be almost compIeteIy excavated by digestion and infection has ThaIIheimer* frequentIy been observed. has shown that the excavation may be compIete Ieaving no trace of the origina carcinoma. I have recentIy observed a case dying from secondary gastric carcinoma of the Iiver, recognized by the characteristic mucus ceIIs with signet ring nucIei, in which the onIy source of the cancer seemed to be a pyIoric uIcer which had been compIeteIy excavated from a11 traces of cancer, I have repeatedIy seen the origina cancer reduced to a narrow ring of tumor tissue Iying just beneath the overhanging edge of the uIcer. Therefore, the presence of isIands of cancer in the edges of an uIcer is no indication that the cancer is the seque1 of the uIcer. The occurrence of muItipIe areas of early cancer in a IocaIized area aIso compIicates the interpretation of cancerous uIcers. If an adenocarcinoma extends IateraIIy by uIceration then it may encounter in-its advance a second or third focus of primary carcinoma. In segments of the uIcer wiI1 then be found points of carcinoma, deveIoping through gradua1 transformation of the gIands on the edge of the ulcer, but these secondary cancers wiI1 have had nothing to do with the original cancer or uIcer. They are a11 primary independent cancers. These considerations reIating to the excavation of earIy adenocarcinoma and of the occurrence of muItipIe primary foci of carcinoma, seem not to have been fuIIy evaIuated by those who favor the frequent deveIopment of cancer on uIcer. *Ann.
Surg.,
67, zrq, 1918.
EWING,
CANCER*
M.D.
Director, The MemoriaI HospitaI NEW
A
YORK,
accurate knowIedge of the beginnings of gastric cancer wouId direct the search for the earIy curabIe stages of the disease, probabIy throw Iight on the causation, and expIain many of the cIinica1 pecuIiaritiks. The most important contribution on this subject is that of Ver.4, from Marchand’s Iaboratory, (Arbeit, p. Instit. Leipsig, 190% 5, I.) Among 10,000 autopsies Verst: encountered I 2 earIyg astric cancers, unsuspected during Iife. They were usuaIIy smaI1, 0.5 to 5 ems. in diameter, circumscribed, sIightIy eIevated, sometimes eroded, infected, infiItrated with Ieucocytes, and a11 were adenocarcinomas. In several cases there was genera1 atrophic or hyperpIastic gastritis, and a history of aIcohoIism. It is thus apparent that gastric cancer often begins as a IocaIized overgrowth affecting primariIy previousIy norma ceIIs which show atypical overnutrition and overgrowth, and that infection, erosion and uIceration may supervene very earIy. I have seen three such cases at autopsy which presented the above structure. Rather different was the condition in a remarkabIe case of which I have seen onIy one exampIe. The antra1 mucosa was the seat of a foca1 hyperpIastic gastritis affecting much of this region. The gIands were moderateIy enlarged and the Iining ceIIs hyperchromatic. At many points over this area there were erosions of sIightIy eIevated patches, and here the gIands were distinctIy atypica1, hyperplastic, and beginning to invade through the muscuIaris mucosae. This was an earIy superficia1 adenocarcinoma arising at muItipIe points over a rather wide area of hyperpIastic gastritis. If this condition had progressed, it wouId probabIy have resuIted in a Iarge region of superficia1 N
* Read at a RoundTabIqConference
oncancer
N.
Y.
erosion with gradua1 extension of the disease through a11 coats of the stomach. I suspect that this is the mode of origin of many of the superfica1 erosive carcinomas of the pyIoric antrum in which there is no IocaIized tumor or uIcer, but onIy diffuse erosion of the mucosa and infiItration of the submucosa. It is a nice question over which to ponder:-what can be the cause of such a pecuIiar atypica1 hyperpIastic gastritis? It is not the usua1 chronic hypertrophic form of gastritis, with greatIy enIarged gIands and increased stroma, but one which is highIy atypica1 from the first and runs rapidIy into cancer. It suggests the IocaI action of some strongIy cancerigenie irritant. I have seen the same type of hyperpIastic gIanduIar inff ammation in the rectum which was the seat of carcinoma. The early Iiterature on gastric cancer shows that the deveIopment of adenocarcinoma from muItipIe foci has frequentIy been observed, especiaIIy by WaIdeyer and by Hauser, usuaIIy fron rather we11 defined areas with fuI1 deveIoped but smaI1 adenocarcinomas, separated by norma mucosa. The case which I have described showed diffuse atypica1 changes over the entire affected region, without any norma mucosa. Both these processes, especiaIIy the Iatter, probably Iead in Iater stages to the wide superficia1 uIcerating adenocarcinomas occasionaIIy encountered. Some other ways are known in which superficia1 erosive carcinomas begin. There is a group of cases in which the superficial epitheIium and that of the ducts remains intact, but the tubuIar gIand fundi break up and the maIignant epitheIia1 ceIIs infiItrate wideIy over the mucosa. I have pictured two such cases in NeopIastic Diseases. The earIy resuIt is a superficial eroding carcinoma without tumor formation or excavation What the Iater stages
at the Fiftieth Anniversary 204
of the Memorial HospitaI, May
z5,Ig34.
NEW
SERIES VOL. XXX],
No.
z
Ewing-Gastric
may be I do not know. Hayem* has described the development of a diffuse scirrhus or fibrous carcinoma in a case of diffuse parenchymatous gastritis in which the peptic gIands seemed to break down and the granuIar acidophiIe peptic ceIIs spread through the stroma giving origin to the cancer. I have seen one early eroding cancer which recaIIed this description. From the morphoIogy of these earIy eroding superfica1 carcinomas one may draw certain concIusions of practica1 interest. When the superficia1 Iining ceIIs remain intact one can hardIy assume that the process resuIts from the action of superficial irritants. It must arise from factors affecting the tubuIar portions of the gIands excIusiveIy and be referred to some other much more subtle and probably intrinsic factors. Since a Iarge proportion of the gastric cancers are superficia1 and mereIy erosive in their earIy stages they wiII probabIy not be reveaIed to the radioIogist by any definite tumefaction or by any fiIIing defect, but must be found, if at aI1, by some other criterion. It may be suggested that these earIy criteria probabIy take the form of obhteration of the rugae or fixation of the mucosa. CongenitaI or acquired structura1 abnormaIities give rise to a smaII proportion of gastric cancers. Heterotopias of intestinal mucosa are frequentiy found in the pyIoric region and some authors have traced uIcers and cancers to this origin. Pancreatic isIands have been found in the stomach waI1 and these must be considered as rare sources of peculiar types of carcinoma. Misplaced isIands of gastric gIands may be found in the stomach waI1. RecentIy Pack discovered almost by accident, by a thorough, very minute inspection of x-ray plates taken by Dr. Hauser, and removed a smaI1 fulIy maIignant smaI1 ceI1 adenocarcinomatous noduIe deep in the submucosa of an otherwise norma stomach. Carcinoma arising in the ordinary type of chronic hypertrophic gastritis seems to be rare, aIthough Konjetzny frequentIy finds gIand heterotopia. In the poIypoid form of chronic gastritis singIe or muItipIe * Hayem, G. Rd. WC. anat. 1905, 80, 649.
Cancer
Beginnings
A me&m
Journal of Surgery
205
carcinomas are frequent, and the natura1 termination of this disease in the stomach, as in the colon, is death from cancer. SoIitary poIypoid adenomas and Iow grade adenocarcinomas give rise to the very characteristic buIky maIignant tumors of the stomach which give unexpectedIy good resuIts from resection. Their detection in the earIy stages is readiIy accompIished. These observations on earIy gastric cancer have a bearing on the subject of uIcero-cancer. It appears that adenocarcinomas tend to uIcerate at a very earIy stage. That they may be almost compIeteIy excavated by digestion and infection has ThaIIheimer* frequentIy been observed. has shown that the excavation may be compIete Ieaving no trace of the origina carcinoma. I have recentIy observed a case dying from secondary gastric carcinoma of the Iiver, recognized by the characteristic mucus ceIIs with signet ring nucIei, in which the onIy source of the cancer seemed to be a pyIoric uIcer which had been compIeteIy excavated from a11 traces of cancer, I have repeatedIy seen the origina cancer reduced to a narrow ring of tumor tissue Iying just beneath the overhanging edge of the uIcer. Therefore, the presence of isIands of cancer in the edges of an uIcer is no indication that the cancer is the seque1 of the uIcer. The occurrence of muItipIe areas of early cancer in a IocaIized area aIso compIicates the interpretation of cancerous uIcers. If an adenocarcinoma extends IateraIIy by uIceration then it may encounter in-its advance a second or third focus of primary carcinoma. In segments of the uIcer wiI1 then be found points of carcinoma, deveIoping through gradua1 transformation of the gIands on the edge of the ulcer, but these secondary cancers wiI1 have had nothing to do with the original cancer or uIcer. They are a11 primary independent cancers. These considerations reIating to the excavation of earIy adenocarcinoma and of the occurrence of muItipIe primary foci of carcinoma, seem not to have been fuIIy evaIuated by those who favor the frequent deveIopment of cancer on uIcer. *Ann.
Surg.,
67, zrq, 1918.