Leiomyosarcoma of Meckel\'s diverticulum

LEIOMYOSARCOMA OF MECKEL’S DIVERTICULUM O L A V A.

HAUGEN,MD, CHRISTOPHER s. PEGG,MB, CHM, FRCS, AND JAMES

KYLE, MCH, FRCS

Two patients with leiomyosarcoma of Meckel’s diverticulum are reported. The natural history of these tumors may extend over many years. Initially, the histologic appearances are those of a benign smooth-muscle tumor, but, eventually, local metastases appear within the peritoneal cavity. Resection of the tumor with adjacent ileum, if not curative, does give relief of symptoms for some years.

M

ECKEL’S DIVERTICULUM,

THE REMNANT OF

the vitello-intestinal duct that persists in about 2% of the population, is almost always a symptomless appendage. T h e few patients in whom it does cause symptoms are usually infants or children. Mechanical obstruction and intussusception, inflammation, and peptic ulceration in or near the diverticulum are the lesions most often encountered. Rarely are these complications found in middle-aged or elderly subjects; however, it is in the older age groups that neoplasms arise. Carcinoids and adenocarcinomas of Meckel’s diverticulum do occur, but because of its long natural history and seemingly benign histologic appearance, the most interesting neoplasm is the leiomyosarcoma. This type of sarcoma is said to be the most common neoplasm of a Meckel’s diverticulum.1l However, only 42 cases have been reported in the world literature, while the total number of carcinoid tumors recorded is 39.12 CASEREPORTS Case 1. A 33-year-old woman was admitted to hospital in January 1938, complaining of recurrent pain and swelling in her right iliac fossa for 3% years. She stated that about 8 years previously she had had melena, but that radiologic investigations at that time (1929) had failed to reveal the cause of the bleeding. On examination, a slightly tender rounded From the Departments of Pathology and Surgery, University of Aberdeen, Scotland, and Ulleval Hospital, Oslo, Norway. Address for reprints: James Kyle, MCh, FRCS, Woodend General Hospital, Aberdeen, AB9 ZYS, Scotland. Received for publication March 16, 1970.

mass about 8 cm in diameter was palpable on the lower right side of the abdomen. At operation, the tumor was found in the distal half of a Meckel’s diverticulum (Fig. 1) which arose from the side of the lower ileum about 30 cm proximal to the ileocecal valve. Large blood vessels passing to the anterior abdominal wall were stretched over the tumor. There was no evidence of metastases. T h e tumor was excised along with an ellipse of intestinal wall; the ileal defect was repaired transversely in 2 layers. T h e right tube and ovary were also removed. Recovery was uneventful. T h e pathologic examination revealed a large necrotic cavity in the center of the tumor: the cavity did not communicate with the lumen of the diverticulum whose wall contained some intestinal glands but no gastric mucosa (Fig. 2). T h e neoplasm was considered to possess the histologic characteristics of a cellular leiomyoma (Fig. 3). Very few mitotic figures were observed, and the appearances were not thought to justify a diagnosis of leiomyosarcoma. T h e patient was next seen in October 1947, complaining of discomfort and a mass in the left iliac fossa. Her health had been reasonably good during the period of almost 10 years since her first operation. However, laparotomy revealed an irremovable mass on the left side of the abdomen and several large metastatic nodules in both lobes of her liver. A biopsy was taken from one of these nodules and the abdomen was closed. T h e patient returned home on the 14th postoperative day. O n this occasion, histologic examination revealed a neoplasm similar in structure to the one removed 10 years earlier; with van Gieson and phosphotungstic acid-hematoxylin stains, the tumor was shown to have arisen from smooth niuscle and fibrous tissue. There was more nuclear pleomorphism

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amination there was little cellular aberration. Although the appearances were less differentiated than those noted in the liver lesions 2 years earlier, mitoses were extremely scanty. Invasion of fatty tissue was noted. T h e patient eventually died from hepatic metastases in December 1950. No autopsy was obtained.

FIG. 1 Leiom)osarcoma of Meckel’s diverticulum: diagram of the appearances in Case 1 when the tumor was lifted up. The vitello-intestinal vessels passing in a fold of the mesentery across the tumor to the abdominal wall are characteristic. The tumor has been opened to show its central cavity (upper arrow) which is separate from the lumen of the diverticulum (lower arrow).

than in 1938, and some cells showed a high nucleocytoplasmic ratio, suggesting that now the tumor was growing more actively. However, mitotic figures were still scanty-less than one per high-power field. T h e neoplasm was considered to be sarcomatous (Fig. 4). Two years later, in November 1949, the patient was re-admitted. For 10 weeks she had been feeling tired and had had frequency of micturition and a dragging sensation in her lower abdomen. Her bowels were functioning normally. A large, slightly mobile mass was palpable in the suprapubic region, but her liver did not appear to be enlarged. At operation, the central abdominal tumor was very hemorrhagic, involved several loops of small intestine, and appeared to extend back into the retroperitoneum. I n addition, there were numerous small metastases widely scattered throughout the visceral and parietal peritoneum and omentum; one of these metastases was excised. Even at this late stage, on histologic ex-

Case 2. A 39-year-old man was first seen in July 1968, complaining of colicky right lower abdominal pain present intermittently for 2 years. O n occasion, the patient had noticed a lump just lateral to the lower right rectus muscle; he stated that by pressing on the lump he could make it disappear with a gurgling sensation. He had lost 7 lb. (3 kg) in weight in the preceding 6 months. Physical examination was negative, but the possibility of an interparietal hernia was considered and operation advised. When admitted 4 weeks later, the patient stated that he had been having melena; his hemoglobin was 8.4 g per 100 ml blood. At operation, an ovoid tumor measuring 20 x 12 x 12 cm was found arising from a Meckel’s diverticulum of the lower ileum (Fig. 5 ) . T h e base of the diverticulum was overhung by the tumor which had large vitello-intestinal vessels passing over its surface. Several small pearly nodules 3-6 mm in diameter were seen on the adjacent wall of the ileum. No distant metastases were found, and the liver felt normal. T h e tumor was excised along with a 7-cm segment of ileum, continuity being reestablished by end-to-end anastomosis. One of the more distant small nodules was also removed for examination. T h e immediate postoperative course was uneventful, and the patient returned home on the 11th day. Fifteen months later he is symptom-free, with a normal hemoglobin level and a negative stool toluidine test. Pathologic examination showed that the center of the tumor was necrotic and cystic. I n the proximal part of the specimen there was a Meckel’s diverticulum arising from the ileum, but its lumen did not communicate with the cystic cavity. Histologic sections of the tumor showed a fibrocystic wall (Fig. 6) with extensive areas of necrotic material on the inner surface and widespread areas of hemorrhage. I n the better preserved areas, the neoplasm showed a whorled pattern; it was composed of spindle-shaped ceIIs alternating with plumper or round cells with nuclear atypia (Fig. 7). Few mitotic figures were seen. Examination of sections stained with van Gieson, and phosphotungstic acidhematoxylin stains confirmed the provisional histologic diagnosis of leiomyosarcoma. Sections of the small nodule revealed cells similar to those in the main tumor, which,

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FIG.2. Case 1. Primary tumor showing a rather cellular lesion with pseudocapsule. Note diverticulum is lined with mucosa of small bowel type (left), H and E, x120.

FIG. 3. Case 1. Primary tumor consisting of uniform spindleshaped cells with the occasional plump cell (H and E, xS00).

7, 8, 10 which, along with our 2 cases and Lie’s case,6 bring the total to 44. Most published reports on disease of Meckel’s diverticulum emanate from childrens’ hospitals, where maDISCUSSION lignant neoplasms are relatively uncommon. In reporting one case in 1966, Lie6 reviewed A large sarcoma in an adult is likely to be the literature on leiomyosarcoma of Meckel’s reported, but some are very small. T h e one diverticulum and collected 34 other examples described by Carroll4 was a surprise findof this rare tumor. This total included 32 out ing during the examination of a resected of the 35 sarcomas of Meckel’s diverticulum gangrenous diverticulum. Leiomyosarcoma appears to develop in contained in the review published by Weinstein, Dockerty, and Waughll; the only other Meckel’s diverticula in patients over the age distinctive type that these authors recognized of 20 years. Sailer and his colleagues,s in was the lymphosarcoma. I t is surprising that Germany, reviewed the personal details of 20 reticulum cell sarcoma has never been de- reported cases. Their ages ranged from 22 scribed in a Meckel’s diverticulum, since it is years to 81 years; 17 were more than 40 years the most common malignant neoplasm of the old. The sexes were affected equally. Lower small intestine.2 During the last 2 years, 7 abdominal pain was the most common sympmore leiomyosarcomas have been r e p ~ r t e d ,50~ . tom, closely followed by intestinal bleeding.

however, contained more than twice as many cells per high-power field.

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FIG.4. Case 1. Liver metastasis. Note cellular pleomorphisrn (H and E, ~ 1 2 0 ) .

Obstruction developed in some cases and, occasionally, the patient had noticed a tumor. At least 2 tumors were palpable on rectal examination; almost certainly the tumor in case 2 periodically disappeared into the pelvis where it could have been felt through the rectum. One of the 2 leiomyosarcomas reported by Tzanev and Popdimitrovlo perforated, causing an acute abdominal emergency. At operation, it may be difficult to identify any uninvolved part of the Meckel’s diverticulum when the tumor is large. However, the position of the tumor close to but separate from the side of the lower ileum and the presence of large vitello-intestinal blood vessels, as shown in Fig. 1, should suggest the correct diagnosis. I n each of our cases, the orifice of

the diverticulum was visible when the resected ileum was opened, and histologic examination showed intestinal glands in what remained of its lining mucosa. Central necrosis and cystic degeneration of the tumor appear to be common findings. Although there may be an attempt at pseudocapsule formation, local infiltration sometimes takes place, and there may be seedlings on adjacent intestine. However, such evidence of spread is slow to appear, and distant metastases are unusual. It is in the histologic interpretation of leiomyosarcomas that the greatest difficulties are encountered. A neoplasm whose cellular characteristics would be judged benign on normally accepted criteria may, after the lapse of

FIG.5. Case 2. Leiomyosarcoma of a Meckel’s diverticulum (arrows).

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FIG. 6. Case 2. Diverticulum lined by small bowel mucosa with a cellular, well-circumscribed tumor in the wall (right), H and E, ~ 3 0 .

FIG. 7. Case 2. Predominant cell type of tumor: spindles h a p e d cells with a b u n d a n t cytoplasm. Mitoses are absent (H and E, x300).

5 or 10 years, be found to be spreading locally in the peritoneal cavity. On pure histologic criteria, a diagnosis of malignancy could not be easily given in either of our cases since they were well-differentiated tumors with few mitotic figures and tumor giant cells. There was greater cellularity and more marked pleomorphism in case 2 than in case 1. However, it was mainly in the central parts of the tumor that pleomorphism was present, and this could perhaps be explained in part by degenerative changes in relation to the cystic areas of the tumor. I t has been suggested by Starrg that the best histologic criterion of malignancy is the presence of mitotic activity, with cellularity and pleomorphism as supporting factors. dn neither of our cases has the mitotic activity

been of any help at all in establishing the diagnosis of malignancy. Starr also gives a very rough estimate of the likelihood of malignancy according to the size of the tumors in that no benign tumor in his series was found to be larger than 7 x 5 x 5 cm and no malignant lesion smaller than 2 x 2 x 1 cm. Unfortunately, many tumors may lie between these limits so that size alone is of little help in determining malignancy. T h e histologic features of these neoplasms are those of a low-grade malignant neoplasm in which a prolonged course can be anticipated. I n our case 1, the correct diagnosis could be given only in retrospect. T h e sections from the liver did show tumor cells with marked atypia, while a later section from the mesentery had less atypia. Our case 1 in-

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dicates that the prognosis of smooth muscle tumors of the intestinal tract should be given with great caution especially when dealing with the larger tumors. T h e histologic appearance of the small nodule removed in case 2 was very similar to that of a benign leiomyoma. While the presence of several serosal nodules might suggest multicentric neoplastic development, their proximity to a very large malignant neoplasm strongly suggests that they are metastases in spite of their less cellular appearance. Out of 25 smooth-muscle tumors of the alimentary tract reported from this center,3 13 were classified as benign leiomyomas. Why have such benign tumors so rarely been reported in a Meckel’s diverticulum? Allegedly benign smooth muscle tumors of the stomach and intestines are generally regarded with great suspicion, since it is believed that many of them will in time by their progression eventually reveal themselves to be malignant. If this clinical suspicion is correct, then it is possible that a seemingly benign tumor might exist and grow slowly for some years in a “lay-by” such as a Meckel’s diverticulum without giving rise to any symptoms; only later would symptoms such as bleeding and intestinal obstruction become manifest. By contrast, for mechanical reasons, even a small tumor in the wall of the small intestine proper must reveal its presence at an earlier date, be excised, and then be classified as “benign.” Excision of the leiomyosarcoma in conti-

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nuity with a portion of contiguous ileum is the treatment of choice. When multiple nodules are present, radical excision of all involved intestine may not be possible. Welldifferentiated leiomyosarcomas are not sensitive to radiotherapy or cytotoxic drugs. Sailer and his colleagues8 did instill radiogold into the peritoneal cavity in an attempt to prevent implantation of sarcomatous cells accidentally spilled in the course of their operation. Curative surgery is not possible in approximately one third of patients with Ieiomyosarcomas of Meckel’s diverticulum. Published follow-up studies are very few, but for leiomyosarcomas of the small intestine about half the patients are alive at the end of 5 years. T h e results may not be so good for such tumors in diverticula, because, in the latter situation, the tumor is likely to have reached a more advanced stage by the time it is first detected. Nevertheless, case 1 survived at least 12 years after the diagnosis of the tumor. Indeed, the tumor may well have been presnnt 8 years earlier when the patient had melena. There seems little doubt that the melena was due to some complication of a Meckel’s diverticulum and, since n o gastric mucosa was detected in the resected specimen, peptic ulceration of the adjacent ileum is unlikely to have been responsible. Although there can bc no guarantee of cure in leiomyosarcoma of Meckel’s diverticulum, the chances of longterm survival after resection are good.

REFERENCES 1. Rosciano, N.: Leiomioma in diverticolo di Meckel perforato. Policlinico (Prat.) 67:589-590, 1960. 2. Brookes, V. S.: Malignant tumours of the small intestine. Proc. Roy. Soc. M e d . 61:216-217, 1968. 3. Bruce, A. W., and Stalker, A. L.: Smooth-miiscle tumours of the alimentary tract. Brit. J. Surg. 46:629F33, 1959. 4. Carroll, K. J.: Malignant tumours of Meckel’s diverticulum-case report of a leiomysarcoma. Postgrad. M e d . .I. 42:275-276, 1966. 5 . Ginbbo!ini, G., d e Nauro, D., and Musiani, R.: Leiomiosarcoma del diverticolo d i Meckel. G . Ital. Chir. 22:197-205, 1966. 6. Lie, J. T.: Leiomyosarcoma of Meckel’s diverticulum. Brit. J. Surg. 53:336-339, 1966. 7. Root, G. T., and Baker, C. P.: Complications

associated with Meckel’s diverticulum. Arner. J . Surg. 114:285-288, 1967. 8. Sailer, R., Bohme, H., and Jacobs, G.: Leiomyosarkom des Meckelschen divertikels. Deutsch. M e d . Wschr. 93:44&450, 1968. 9. Starr, G. F.: Myomatous tumors of the small intestine, benign and malignant. M.D. Thesis, Graduate School, University of Minnesota, 1953. 10. Tzanev, K., and Popdimitrov, 2.: Neoplasia del diverticolo di Meckel. Minerva M e d . 57:2876-2877, 1966. 11. Weinstein, E. C., Dockerty, M. B., and Waugh, J. M.: Neoplasms of Meckel’s diverticulum. Int. Ahstr. Surg. 116:103-111, 1963. 12. Weitzner, S.: Carcinoid of Meckcl’s Diverticulum. Cancer 23:1436-1440, 1969.