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THE AMERICAN JOURNAL of CANCER a Continuation of the Journal of Cancer Research

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THE AMERICAN JOURNAL of CANCER a Continuation of the Journal of Cancer Research THE AMERICAN JOURNAL OF CANCER A Continuation of The Journal of Cancer Research VOLUME XVIII AUGUST,1933 NUMBER4 CARCINOID TUMORS OF THE QASTRO-INTESTINAL TRACT (SO-CALLEDAB~ENTAFFINE TUMORS) THEODORE S. RAIFORD, M.D. (From the Departmanla of Surgery and SurgiWl Pathology, Johns Hopkina Hospital and University) There is perhaps no group of tumors which has been so widely discussed during recent years as the “ carcinoids,” or ‘‘ argen- tathe tumors.’’ While by no means constituting a new patho- logical entity, they present interesting problems of clinical and pathological significance. It is difficult to contribute at this time to the histogenesis of the carcinoids. Masson and others have demonstrated through intensive studies the origin of these tumors from the so-called chromo-argentaffine or Kultschitzky cells of the intestinal mucosa. It is the purpose of this paper to summarize the present knowl- edge and report a group of cases observed in this laboratory, discussing their clinical and pathological significance. In a review of the material in the pathological laboratories of the Johns Hopkins Hospital, 29 carcinoid tumors were found. This number occurred among some 62,000 specimens of all kinds, including autopsy material and specimens removed at operation ; 1,611 of these were tumors of the gastro-intestinal tract, placing the incidence of the carcinoids at 0.18 per cent. HISTORICAL Forbus has presented an excellent and detailed historical re- view of the carcirioid tumors and for those who are interested in 803 804 THEODORE 8. RAIFORD that phase of the subject his article, published in 1925, is recom- mended. He reported in addition 6 cases of carcinoids of the appendix. None of his cases had metastasized, and he, like Obern- dorfer, called attention to their harmless character, A number of metastasizing carcinoids have been reported during recent years. Cooke, summarizing all reported cases occurring in the small intestine, found metastases in 26 per cent. Of his own 11 cases, 27 per cent were malignant. He emphasized the fact that, al- though benign in appearance, the carcinoids frequently metasta- Aize, similar to carcinomas elsewhere in the gastro-intestinal tract. Marangos believes that in time all carcinoids become malignant, due to invasion of the blood vessels by tumor cells, and that the malignancy of the tumor varies with its size. GChspBr agrees, but believes that the tumors may metastasize through the lymphatic system as well. Masson's work on the histogenesis of carcinoids is a valuable contribution and will be considered more fully in a later section. LOCATION The 29 carcinoids observed in this laboratory were distributed throughout the gastro-intestinal tract as follows : Stomach ....................................................... 1 Small Intestine ................................................ 9 Duodenum .............................................. 1 Jejunum ............................................... 1 Ileum .................................................. 7 Appendix .................... ...'............................... 17 Tip .................................................... 12 Middle ................................................. 3 Base ................................................... 2 Large Bowel ................................................... 2 Colon .................................................. 2 Rectum ................................................. 0 TOTAL................................................. 29 The appendix is by far the most common location of carcinoid tumors. The small intestine is the seat of the lesion in approxi- mately half as many cmes, whereas the tumors are of extreme rarity elsewhere in the intestinal tract. Seven of the tumors of this series in the small intestine were located in the terminal ileum and one of those in the colon was in the cecum. The region of the ileocecal valve, therefore, was the site of roughly 85 per cent of the tumors. It is difficult to explain the frequency of carcinoids in the appendix, especially since that organ is so rarely the seat of neoplastic growth. A factor of great clinical importance is that CAROINOID TUMORB OF (tAL3TRO-INTESTINAL TRACT 805 the carcinoids of the appendix usually produce obliteration of the lumen, with consequent symptoms of chronic appendicitis, thereby attracting the early attention of the clinician. It is quite probable that identical tumors in the remainder of the intestinal tract, causing no symptoms, frequently escape discovery. The distri- bution of the chromaffin cells in the intestine may be relevant to the distribution of the tumors, in that these cells are more common in the sites where the tumors are most frequent. This will be discussed more fully under histogenesis. Ago In yawl WQ. 1. CHART SHOWINQ THE AGE0 OF QRMTEET INCIDENCE OF CARCINOlD TUMORS The varioue locations are indicated by different lines. The appendix curve reaches ite peak in the second decade. In sharp contraet to this the curves of tho remaining por- tions of the tract lie entirely between the fifth and eevcnth decades. AGE,RACE, AND SEX Carcinoids are not peculiar to any age group. The oldest patient in this group was sixty-six years of age and the youngest twelve. The average age was thirty-five. In analyzing the cases according to their location, a most interesting observation wa8 made. The appendiceal tumors occurred at an average age of twenty-five year's, while the average ages for carcinoids in the small intestine and the colon were fifty-five and forty-five years respectively. This is illustrated graphically in Figure 1. The appendix curve reaches its peak in the second decade, thereafter 806 THEODORE 8. RAIFORD dropping to zero, while the curves for the small intestine, colon, and stomach reach their peaks in the fifth decade or after. This can be explained on the basis of early recognition of symptoms in FIO. 2 (PATH. NO. 10023, CASE 5). SECTION FROM A SMALL PEDUNCULATED CARCIHOIDIN THE ILEUM Note the isolated tumor nodules, and the overlying intact mucoum membrane. the appendix, as stated above. It would seem, therefore, that carcinoid tumors occur commonly in youth, but are seldom rec- ognized unless so located as to cause acute symptoms, There is nothing significant in the race or sex distribution. CLINICALFEATURES There is little to be said in regard to the distinguishing clinical features of carcinoid tumors. Brief reports of the cases of this series with their outstanding clinical findings are appended. , Stomach and Large Ziztestine: In the stomach, colon, and rec- tum the carcinoids produce the symptoms of any gastro-intestinal tumor. All of the tumors in these organs were malignant. They did not, however, produce the marked general symptoms of malig- nancy-cachexia, anemia, and loss of weight. Diarrhea is of common occurrence, but melena is rare. The presence of these features in one case led a house officer to suggest the diagnosis before operation. This cannot, however, be regarded as a reliable means of diagnosis. No doubt there are many tumors which escape observation. The rate of growth of a carcinoid tumor is extremely slow, and since no symptom is apparent before partial obstruction, a considerable time elapses before the condition is recognized. SmaZZ Zntestilze: The majority of tumors in the small intestine are apparently benign, eausing no symptoms unless of sufficient size to produce obstruction. Two of our nine cases were malig- nant and had metastasized to the lymph nodes and the liver. In CARCINOID TU MOW OF OASTRO-INTESTINAL TRACT 807 such a case obstruction may be recognized early if the lumen of the small bowel is occluded. All of the benign tumors, however, were asymptomatic and were discovered only at autopsy. FIO. 3 (PATH. NO. 47648, CASE 11). DRAWINOOP A CARCINOID OF THE APPENDIX, ACTUAL slZE The grose specimen depicted shows a large, bulbous appendix over which the ves- sels are tortuous and enlarged. There is a small amount of peritoneal fat attached to the specimen. The drawing on the right illustrates sections taken at various levels through the tumor. The tumor consists of a dense growth surrounding the lumen, which is almost entirely occluded. In the two larger sections the fibrous capsule can be plainly seen. (Case of Dr. T. 8. Cullen) FIO. 4 (PATH. NO. 47648, CASE 11). PRonXfRAPH OF SERIAL BLOCKSTJiROUOH THE TUMORSHOWN IN WQ.3 The sections from left to right represent their order in the tumor from base to tip. The tumor is seen to occlude the lumen and is surrounded by a dense fibrous capsule. (Case of Dr. T. 8. Cullen) Appe,ndix: A different situation exists in the appendix. The symptoms are usually those of chronic appendicitis, brought on by obliteration of the appendiceal lumen. This, of course, occurs only when the tumor is of su5cient size; otherwise no symptoms are produced. In a few cases the tumor of the appendix has been so large as to be palpable on physical examination. 808 THEODORE 8. RAIFORD Although considerable work has been done in attempting to establish the relationship of the carcinoids to the endocrine sys- tem, no one has recognized any definite resulting metabolic change. Hence a preoperative diagnosis of the specific type is impossible. PATHOLOGY Gross PnthoEogy: The typical carcinoid tumor is usually recog- nixed as a small nodule in the submucosa of the bowel. It is firm, rubbery, and moves freely beneath the mucous membrane. It may assume a pedunculated form, as in Figure 2. The cut surface has a bright yellow color. In
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