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MALIGNANT FIBROUS MESOTHELIOMA OF THE PERITONEUM
ROBERT P. HILL, M.D.

IN 1942, Stout and Murray reported an exam¬ple of a pleural neoplasm having character¬istics different from those found in tumors orig¬inating in other parts o£ the body. Tissue-cul¬ture studies of this growth were indicative of a mesothelial derivation and the name “local¬ized pleural mesothelioma” was suggested for it. At that time, a comprehensive survey of the literature by them failed to reveal any clear concepts of pleural neoplasms except for the diffuse tubular tumors. They gained the im¬pression, however, that such tumors had been reported under a variety of terms, the different authors failing to realize that they were de¬scribing essentially the same neoplasm, since no one of them had had sufficient material for study to reach such a conclusion. Thus, the con¬cept that fibrous-tissue tumors of the pleura could arise from mesothelial cells instead of the connective tissue of the subserous zone opened the field for re-evaluation of this group. Pursuing the subject further, Stout and Hima-di, in 1951, described in detail seven additional cases incorporating with them the single case already reported. Three of these eight tumors were considered benign, while the other five were believed to be malignant or potentially so. Since no similar growths of peritoneal deri¬vation had been described, Stout1 reported an example involving the peritoneum and having the same clinical and pathological character¬istics as the benign pleural mesotheliomas. Re¬cently, he2 has listed five solitary malignant peritoneal mesotheliomas (including the one reported here) without, however, describing their gross and microscopic appearance.

The following case is reported, since it not only arose from the peritoneum but pursued a malignant course while retain ing the histo-logical features usually associated with the be¬nign pleural and peritoneal mesotheliomas.

CASE REPORT

From  the  Department  of  Pathology,   The   George Washington University Hospital, Washington, D. C. Received for publication, April 13, 1953.
R. D., a 33-year-old white man, was admitted on June 18,1951, with a diagnosis of abdominal tumor. He had been observed elsewhere in June, 1950, because of a sudden attack of intestinal obstruction that subsided spontaneously. Roentgen-ray studies of the gastrointestinal tract after cessation of the obstruction were considered negative. A similar episode occurred one month later, and a repeat gastro¬intestinal examination showed an obstructive lesion of the colon. On abdominal exploration, a large neoplasm in the lower abdomen, apparently external to and compressing the colon, was found. There were numerous peritoneal and mesenteric metastases. The terminal ileum also was compressed by the neoplastic process. An ileostomy was done and biopsies were taken. The tentative diagnosis was leiomyosar-coma, probably retroperitoneal in origin. Two months after surgery, back pain began and gradually increased in severity so that the constant use of narcotics was necessary for the last six months. In March, 1951, symptoms of intestinal obstruction again appeared but sub¬sided with conservative therapy. There had been an 8-lb. weight loss during the course of the illness. Edema of the extremities developed a few weeks before admission.

Physical examination revealed a chronically ill, emaciated man with marked pallor of the mucous membranes. An ileostomy opening was present in the right lower quadrant. The abdomen was protuberant and tense, and a hard, fixed, tender, irregularly nodular mass filled its entire lower part. Multiple, smaller masses of varying size were present in the upper abdomen. There was no apparent ascites. A marked pitting edema was noted in the legs and feet.

Routine laboratory studies on admission were negative except for a moderately severe secondary anemia (volume of packed cells, 26 mm.; hemoglobin, 8.4 gm.), and a low serum albumin (2.87 mg. per 100 cc). A roentgen-ray film of the chest was negative.

The neoplastic disease was considered too far advanced for the usual therapeutic methods, and so it was decided to try intraarterial chemotherapy. On June 19,1951, following multiple whole-blood transfusions, a polyethylene cannula was introduced through the profunda femoris artery so that its tip was well up in the aorta. During the next eleven days, 58 mg. of nitrogen mustard in 2-mg. doses and 20,500 units of aureomycin in 500-unit doses were administered through the cannula. At the end of this period, the nitrogen mustard was dis¬continued, since the bone marrow and peripheral blood were showing a critical depression, but an additional 800 units of aureomycin were given during the next six days. There was no objective or symptomatic improvement from this therapy. By August 5, 1951, the patient was unresponsive, semicomatose, incontinent, and showed spasticity of the neck and extremities. The coma deepened, the blood pressure fell, marked respiratory distress and cyanosis appeared, and he died soon thereafter. Postmortem Examination. Externally, there was slight jaundice, and the cannula was still in place in the left thigh. The abdomen was rounded, protuberant, and multiple hard nodules were palpable throughout. A pitting edema of the legs was noted. On opening the abdominal cavity, about 500 ml. of straw-colored fluid was found. The peritoneum was studded with multiple tumor nodules, and the lower abdomen was filled with a massive tumor incorporating portions of the large and small intestines and the urinary bladder so that these structures could not be separated. These neoplastic masses were coarsely and irregularly nodular and firm. The cut surface was yellowish gray, smooth, and glistening (Figs. 1, 2). Central necrosis with a surrounding zone of calcification was present in some of them. Dis¬section of the large, lower-abdominal mass revealed superficial extension of the neoplasm into the intestinal wall in places and ulceration of the overlying mucosa in one area of the ileum. Several places of partial intestinal obstruction by tumor constriction were apparent. Although closely adherent to the tumor, the wall of the urinary bladder seemed uninvaded. The combined weight of the various nodules was 3820 gm. In the substance of the liver were several metastatic nodules with umbilicated centers measuring up to 2 cm. in diameter. It was impossible to evaluate mesenteric lymph-node involvement because of the presence of numerous tumor nodules in the substance of the mesentery. The paravertebral lymph nodes were negative as was the retro-peritoneum. There was no extension of the disease process outside the abdomen, and other findings were merely incidental.

FIG. 1. A segment of small intestine and mesentery studded with numerous tumor nodules.
FIG. 2. Representative portions of  the principal abdominal mass showing  external  and  cut surfaces.

Microscopic Description

The same general pattern was found in all sections. The basic tumor cell tended to be polygonal or slightly elongated with a round or oval, vesicular nucleus. Cytoplasm was scant and ill-defined. Surrounding individual cells, or clusters of two or three cells, was a lacy net­work of collagenous tissue, the thickness of the collagen fibers varying in different areas (Figs. 3, 4). At the periphery, the tumor was more cellular, but the collagenous network was practically always present. In the central por­tions of the masses, all cells had often disap­peared leaving only the collagenoustissue framework. Some areas were more cellular than others, the individual cells in these in­stances being somewhat larger and more hyperchromatic. Mitoses were exceedingly rare. Sometimes the edges were bounded by a fibrous capsule; elsewhere, although the margin was sharply circumscribed, a capsule was lacking, and occasionally some degree of infiltration was evident either into the capsule or adjacent structures. Lymphatic invasion was present (Fig. 5) and here the cellularity was somewhat greater, but the close association with the col­lagen fibers was still retained. The vascularity was variable, and occasionally the tumor cells in the vicinity of the vessels had disappeared but were still present more peripherally, possibly the result of therapy. The metastatic tumor cells in the liver were essentially similar except that little tendency to a spindle form was found (Fig. 6). Although the collagenous bands were considerably thinner, the basic pattern was preserved.

DISCUSSION
Using the histological criteria previously laid down for the differentiation of benign and malignant fibrous mesotheliomas, the conclusion would be reached that this neoplasm belonged to the benign category. Those tumors described by Stout and Himadi as malignant or potentially so were much more cellular, had fewer reticulin fibers, and no collagen fibers. In this case, the collagenous network was one of the most conspicuous features. After re¬viewing the microscopic sections of this tu¬mor, Stout3 states “in the future I won’t be able to feel so confident that encapsulated tumors projecting into the pleural or peritoneal cavities and having a histological appearance like this one are certainly benign.”

It is believed that initially this neoplasm was a solitary fibrous mesothelioma arising in the lower abdomen and that the multiple peritoneal and mesenteric nodules are metastases rather than an indication of a multicentric origin.

SUMMARY
An example of a fibrous peritoneal mesothelioma having a benign histological appearance but nevertheless producing metastases is reported.

FIG. 3. A typical area in which the tumor cells are enmeshed in a network of thick collagen fibers. (H. & E.)
FIG. 4. A more cellular area, but the collagenous framework is still apparent. The periphery is sharply circumscribed. (H. & E.)
FIG. 5. Infiltration of the wall of the small intestine and lymphatic invasion. (H. & E.)
FIG. 6. A metastasis in the liver. The collagen fibers are much finer but still present. (Masson’s trichrome.)

REFERENCES

1. STOUT, A. P.: Solitary fibrous mesothelioma of the
peritoneum. Cancer 3: 820-825, 1950.
2. STOUT, A. P.: Tumors of the pleura. Harlem Hosp.
Bull. 5: 54-57, 1952.
3. STOUT, A. P.: Personal communication.
4. STOUT, A. P., and HIMADI, G. M.: Solitary (localized) mesothelioma of the pleura. Ann. Surg. 133: 50-64, 1951.
5. STOUT, A. P., and MURRAY, M. R.: Localized pleural mesothelioma; investigation of its characteristics and histogenesis by the method of tissue culture. Arch. Path. 34: 951-964, 1942.