Adenocarcinoid Tumor of the Colon Arising in Preexisting Ulcera tive Colitis

Transcription

1 Adenocarcinoid Tumor of the Colon Arising in Preexisting Ulcera tive Colitis ALAN P. LYSS, MD,* JOHN J. THOMPSON, MD,t AND JOHN H. GLICK, MD* F Patients with ulcerative colitis are at increased risk of developing adenocarcinoma of the colon. The muthors describe a patient whose colonic neoplasm demonstrated histologic characteristics of both an adenocarcinoma and a carcinoid tumor and which was pathologically identical to a appendiceal adenocarcinoid. Because individual tumor cells stained positively for both mucin and srgentaffi granules, the histologic picture is unique among the malignancies seen in patients with ulcerative colitis and cannot be explained as a composite of two independent neoplasms that have grown together. Since the tumor discussed seems to have originated from a single cell Line, the theory that carcinoids develop from neural crest cells which have migrated to embryonic gut endoderm must be regarded with considerable doubt. Cancer 48: , IFTY YEARS HAVE PASSED since Bargen described the first colonic carcinoma occurring in a patient with ulcerative colitis.' Since that time, the population at risk has been more clearly delineated, the pathology of the adenocarcinoma better characterized, and premalignant lesions defined.s Similarly, much information has been gathered about carcinoid tumors which are frequently associated with concomitant, but anatomically separate, gastrointestinal noncarcinoid malignant neopla~ms.~*~~~* In this report, we describe a unique case of a patient with ulcerative colitis whose tumor cells had both carcinoid and adenocarcinomatous features. Case Report A 32-year-old man with a 15-year history of ulcerative colitis which had been well controlled with sulfasalazine was admitted to the hospital because of large bowel obstruction. A barium enema examination demonstrated evidence of chronic pancolitis and a partially obstructing lesion was seen at the splenic flexure. Several additional small polypoid lesions were noted in the sigmoid colon. Laparotomy revealed a splenic flexure tumor with invasion through the serosa. Diffusely scattered miliary nodules were noted on the rnesentery, visceral, and parietal peritoneum, but palpation of the From the * Hematology-Oncology Section, * Department of Medicine, and t Department of Pathology, Hospital of the University of Pennsylvania and the University of Pennsylvania Cancer Center, Philadelphia, Pennsylvania. Supported in part by NCI Grant No. CA Address for reprints: John H. Glick, MD, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA The authors thank Dr. H. T. Enterline for reviewing the manuscript and the pathologic material. Accepted for publication July 30, FIG. 1. Grossly, the patient's colon showed acute changes of active ulcerative colitis in sigmoid and descending colon and cecum. Several inflammatory polyps were noted in sigmoid and ascending colon. Constricting lesion noted on barium enema is seen in the upper left hand comer )</81 /0801 /0833 $ American Cancer Society 833

2 834 CANCER August Vol. 48 FIG. 2. The tumor was composed primarily of signet-ring-type cells with marked much production. Most areas resembled colloid carcinoma. (H & E, x400). liver failed to reveal any abnormality. A total abdominal colectomy with ileoproctostomy was performed and the peritoneal nodules and mesenteric lymph nodes were biopsied. The postoperative course was uncomplicated. The pathologic diagnosis was adenocarcinoid tumor of the colon with peritoneal seeding. One month postoperatively. chemotherapy was begun. The regimen consisted of 5-fluorouracil, 400 mg/m2, and streptozotocin, SO0 mdrn'. Each drug was given intravenously for five days every six weeks. The chemotherapy was well tolerated. The patient felt well, gained 28 pounds in weight over a five-month period, and there was no tumor progression as determined with noninvasive techniques. Six months after undergoing laparotomy, the patient was again hospitalized because of small bowel obstruction. Laparotomy revealed that the distal ileum had been contorted by fibrous tissue and it appeared to be ischemic. In addition, the size of the peritoneal nodules had increased. The ischemic portions of ileum were removed and an ileostomy and rectal mucus fistula were created. Over the next two months, the patient's alkaline phosphatase level rose and a repeat abdominal sonographic examination showed peripancreatic nodal enlargement. In addition, a repeat small bowel barium study showed evidence of external compression at the third portion of the duodenum. Results of both studies had previously been negative. Gross Examination Pathologic Results The entire intraperitoneal portion of the colon, a small portion of distal ileum, and several peritoneal

3 No. 3 ADENOCARCINOID TUMOR. Lyss PI ul. 835 FIG. 3. In some areas, tumor cells formed solid islands suggestive of carcinoid differentiation (H & E, X 160). and omental nodules obtained at the original laparotomy were examined. The colon had undergone diffuse mucosal inflammatory changes from the sigmoid margin to the ileal margin with some areas showing more acute ulceration (Fig. 1). The sigmoid and descending colon showed marked shortening with loss of haustrae. At the splenic flexure, a constricting lesion measuring 7 x 5.5 cm obstructed the lumen. The colon proximal to the lesion was markedly dilated. The tumor appeared to be largely intramural and was associated with marked fibrosis. The tumor permeated the wall and extended to the serosal surface. There were numerous small tumor implants over the serosal surface of the sigmoid, descending, transverse, and ascending colon. Several inflammatory polyps were noted in the sigmoid colon and ascending colon. Numerous grossly positive lymph nodes were present. Microscopic Examinution Examination of tumor sections demonstrated the presence of an invasive lesion composed of signet ring cells. In most areas, the tumor had produced large quantities of mucin so that the lesion appeared to be a colloid carcinoma (Fig. 2). In other areas, the tumor cells had aggregated into solid balls or ribbon-like forms, suggestive of carcinoid tumor (Fig. 3). The tumor had freely infiltrated the muscularis propria and had extended to the serosal surface. There had been extensive permeation of the lymphatics, 17 of 66

4 836 CANCER August I 1981 Vol. 48 FIG. 4. Numerous signet-ring-type cells stained positive for both mucin and argyrophil and argentaffn, (composite Grimelius mucicarmine, x 400). lymph nodes, the omentum, and numerous peritoneal nodules along the entire length of the colon. Special stains included mucicarmine for mucin, alcianblue PAS for acid mucopolysaccharides, Grimelius and Sevier-Munger for argyrophilic granules, Fontana and Schmorl for argentaffin granules. All were positive. In addition, Sevier-Munger, Grimelius, and Fontana stains were each performed with both mucicarmine and alcian-blue PAS as a counterstain. These stains demonstrated single signet cells producing both mucin and carcinoid granules (Fig. 4). Examination of sections from one of the sigmoid polyps noted on the radiographs demonstrated the presence of a microinvasive adenocarcinoma of mark- edly different histologic appearance. This second polypoid tumor had formed easily recognizable glands and staining with both argentaffin and argyrophil was negative (Fig. 5). Histologic examination of sections obtained far from the carcinoma demonstrated classic changes of ulcerative colitis. Marked mucosal and submucosal capillary dilatation was noted in conjunction with both acute and chronic inflammation. Crypt abscesses were common. In most areas, mucin production had decreased markedly and the numbers of Paneth cells had increased. Examination of other sections showed areas of ulceration and inflammatory polyp formation. In retrospect, the results of a rectal biopsy, exami-

5 No. 3 ADENOCARCINOID TUMOR * Lyss et al. 837 FIG. 5. Cytologically, the microinvasive sigmoid tumor appeared to be moderately differentiated adenocarcinoma of markedly different type than the large obstructing lesion. Argyrophil and argentaffin stains were negative (H & E, x400). nation performed just prior to the laparotomy were significant. Although the biopsy had shown some fibrosis in the lamina propria and architectural abnormalities of the glands suggestive of healed colitis, there had been no suggestion of the dysplastic changes of Morson and Pang (Fig. 6). Discussion In 1963, Gibbs4 described a rectal lesion which had light microscopic features of both adenocarcinoma and a carcinoid tumor. Special staining had demonstrated intracellular mucin positivity and argentaffin granules in similar locations within the tumor. but not necessar- ily in the same cell^.^ That lesion differed from the two colonic lesions subsequently reported by Bates and Belter2 which demonstrated mucin positivity only in areas without argentaffin granules.2 Toker l1 described three tumors, two of which were colonic, which had intermingling morphologic features of both adenocarcinoma and carcinoid malignancies. However, those neoplasms were negative for both argentaffin and argyrophil staining and therefore a statement cannot be made regarding whether each individual cell showed features of both tumors. The same comment applies to the five intestinal tumors reported by Hernandez and Reid.7

6 838 CANCER August Vol. 48 FIG. 6. Rectal biopsy done prior to resection showed some increased fibrous tissue in lamina propria and gland distortion suggestive of healed or inactive colitis. No suggestion of dysplastic change was found (H & E X 160). In 1967, Gibbs5 demonstrated both argentaffin and Paneth cells in epithelial neoplasms of the large intestine, including adenomas and adenocarcinomas. Two basic patterns were observed: in some cases, the argentaffin-positive cells had occurred only at the base of residual crypts and probably represented nonneoplastic cells surrounded by tumor. However, in other lesions, argentaffin-positive cells were scattered diffusely through the tumor.5 Gibbs felt that these cells were derived from the tumor itself. Subsequently, Drut3 reported one case which had argyrophilic granules in the inspissated mucus of many cells in an ascending colonic lesion. Our patient s tumor had histologic elements of both an adenocarcinoma, and carcinoid and arose against a background of ulcerative colitis. Such a case of ulcerative colitis involving a carcinoidlike characteristic of an adenocarcinoma has not been previously reported, nor has a metastatic carcinoid tumor been noted in a patient with ulcerative colitis. Although the appearance of his malignancy fits the description of the well known appendiceal adeno~arcinoid, ~ the biologic behavior in this case was markedly more aggressive. It is doubtful that the primary neoplasm represented two independent carcinomas which grew together, i.e., a collision tumor, in view of the histochemistry of the cells of the primary and the metastases. At issue is the embryologic origin of carcinoid tumor cells. The evidence reviewed by Skrabanek et all0 for the common origin of carcinoids, oat cell carcinomas,

7 No. 3 ADENOCARCINOID TUMOR Lyss et al. 839 and neural crest tumors under the category of APUDomas is compelling. They have suggested that a common precursor cell may give rise to an oat cell tumor or to a more specialized progeny of epinephrine- and serotonin-producing cells, any of which may produce a variety of hormones on rare occasions. They have acknowledged, however, that no agreement has been reached concerning the origin of the adenocarcinoid tumors. They have rejected the hypothesis that the existence of such malignancies necessarily points to the common origin of the Kulchitsky cell and the adenocarcinoma cell and have admited that whether the Kulchitsky cells arise from neuroectoderm or gastrointestinal endoderm is still unresolved. lo The hypotheses7 advanced to account for composite malignancies include: (1) that such tumors represent coincindental malignant changes in two adult cell types; (2) that a field of neoplastic change is induced by a local carcinogenic stimulus which then promotes dedifferentiation of multiple cell lines present in the field (a particularly attractive theory in a patient such as ours, who had an underlying disease strongly associated with subsequent malignancy); and (3) that the two elements differentiated from a common precursor and the malignancy represent neoplastic change in the precursor cell. We believe that the morphologic and histochemical data presented support of the last theory as the most likely mechanism for the development of the adenocarcinoid colonic tumor in our patient. REFERENCES 1. Bargen JA. Chronic ulcerative colitis associated with a malignant disease. Arch Surg 1928; Bates HR, Belter LF. Composite carcinoid tumor (argentafiinoma-adenocarcinoma) of the colon: Report of two cases. Dis Col Rect 1967; 10: Drut R. Argyrophil mucus-secreting adenocarcinoma of the colon and sobocystomatosis: Report of a case. Dis Col Rect 1974; 17: Gibbs NM. The histogenesis of carcinoid tumors of the rectum. J. Clin Pathol 1963; 16: Gibbs NM. Incidence and significance of argentafiin and Paneth cells in some tumors of the large intestine. J Clin Pathol 1967; 20: Godwin JD. Carcinoid tumors: An analysis of 2837 cases. Cancer 1975; Hernandez FJ, Reid JD. Mixed carcinoid and mucus-secreting intestinal tumors. Arch Pathol 1969; 88: Morson BC, Pang L. Rectal biopsy as an aid to cancer control in ulcerative colitis. Gut 1967; 8: Peskin GW, Kaplan EL. The surgery of carcinoid tumors. Surg Clin North Am 1969; 49: Skrabanek P et al. Unifying concept of non-pituitary ACTHsecreting tumors. Cancer 42: , Toker C. Observations on the composition of certain colonic tumors. Cancer 1969; 24: Teitelbaum SL. The carcinoid-a collective review. Am I Surg 1972; 123: Warkel RL. Adenocarcinoid, a mucin-producing carcinoid tumor of the appendix: A study of 39 cases. Cancer 1978; 42: