Document DMoYjYJMR3k8YOpko4YJ7bkqN

Well-Differentiated Papillary Mesothelioma of the Peritoneum A Cfinicopathologic Study of 22 Cases DEAN DAYA. MD, FRCP(C),' AND W. T. ELLIOTT McCAUGHEY, MD, FRCP{C)t Twenty-two cases of well-differentiated papillary mesothelioma of the peritoneum (WDPMP) are described. Eighteen ofthe 22 patients were women. The peritoneal tumor was usually multifocal. Many of the tumors appear to be indolent or inactive and for practical purposes are benign. However, a few patients receiving adjuvant therapy have died under circumstances that make it difficult to determine whether the tumor was responsible for the death. It is suggested that adjuvant therapy be withheld from patients with WDPMP, unless there is dear evidence of progression. The cause of these rare tumors is not apparent, although three patients had had possible exposure to asbestos and two were sisters. Cancer 65:292-296, 1990. lthough diffuse malignant mesothelioma is been reviewed by the US-Canadian Mesothelioma Panel A a highly malignant cancer, there are other forms of had had immunostaining for keratin, carrinoembryonic mesothelial neoplasm that are much less aggressive or araentigen (CEA), Leu MI, and HMFG-2, Follow-up infor benign. These include multicystic mesothelioma,1 adeno- mation was obtained for 18 cases. Six cases have been `matoid tumor, and the histogenetically contentious lo reported previously.2 calized fibrous mesothelioma. Not as well known is the well-differentiated papillary mesothelioma of the perito Results neum (WDPMP). From the small number of examples described, it would appear that WDPMP is usually an indolent tumor that occurs mostly in women.2"7 Table 1 summarizes the salient clinical and pathologic findings of the cases. In this report, we describe our experience with 22 WDPMP tumors. Clinical Features The ages of the 22 patients ranged from 25 to 69 years, Patients and Methods (average age, 41 years; median age, 40 years). Eighteen, patients (82%) were women (Patients 1 through 18) and The 22 cases were obtained from the Canadian Ref four patients (18%) were men (Patients 19 through 22). erence Centre for Cancer Pathology, Ottawa, Ontario, The lesions were usually discovered incidentally during Canada, and from the consultation files of one of us surgery for conditions such as gallstones, hernia, or aortic; (W.T.E.M.). Between two and 17 hematoxylin and eosin aneurysm, but some patients had abdominal pain, weight (H & E}-stained slides were available in each case. Stains loss, or evidence of"chronic pelvic inflammatory disease." ; for mucin (mucicarmine or periodic acid-Schiff [PAS]) Occasionally, ascites was present. Two patients were sisters had been performed in eight cases. Four cases that had (Patients 6 and 9). From the 'Department of Pathology and Obstetrics and Gynecology, Henderson General Hospital and McMaster University, Hamilton, On tario, Canada; and the fCanadian Reference Centre for Cancer Pathology, Ottawa Civic Hospital and University ofOttawa, Ottawa, Ontario, Can ada. The authors thank Ann Shields, Jean Mattinson, and Joan Stansell for typing the manuscript; Dr. Michael Goodyear for a critical analysis ofthis paper; and many pathologists in Canada and the US for referring ascs and for providing follow-up information. Address for reprints: Dean Daya, MD, Department of Pathology and Obstetrics and Gynecology, Henderson Genera] Hospital, Hamilton, Ontario, Canada. Accepted for publication July 21, 1989. Gross Pathologic Findings ' In most patients, there were multiple omental and pel vic tumor nodules. From the limited information avail-. able, the size ofthese nodules was obviously variable. Most of them appeared to have been in the 0.5-cm to 2.0-cm range, but in many the largest nodules were at least several centimeters in diameter. Sometimes the tumor nodules were described as "papillary." In two patients, the serosal nodules were solitary. Four of the 18 female patients had small tumor fod on the ovarian surfaces, in addition to 292 Table 1. Clinical, Pathologic, and Follow-Up Data on 22 Cases ofWDPMP Age (yr) Sex Clinical manifestations Gross findings Treatment l 60 F Incidental finding at Calcified nodule, omentum Nil cholecystectomy (4 X 3.2 x 2.5 cm) + several small nodules j in pelvis Normal ovaries 2 41 F Chronic pelvic Nodules in omentum and Nil inflammatory disease pelvis 3 4 5 6 7 8 9 10 11 12 13 14 15 28 F 29 F 57 F 39 F 41 F 35 F 35 F 37 43 . F F 45 F 39 F 48 F 69 F Chronic pelvic inflammatory disease Right lower quadrant pain Ascites Incidental finding at cholecystectomy Intestinal adhesions Ectopic pregnancy Abdominal pain Menorrhagia Intermittent abdominal pain Menorrhagia and left adnexal mass MenoiThagia Incidental finding of tumor nodules at hysterectomy for menorrhagia Ascites Left ovarian mass Nodules (1.5 X 2.1 cm) omentum Pelvic adhesions Normal ovaries Tumor nodules 2.5 cm maximum diameter Diffuse tumor, peritoneum (2 cm nodules) Cystic ovaries, not removed Omental nodules Normal ovaries Papillary lesions mesentery Normal ovaries and uterus Nodule' on right fallopian tube Tumor nodules cul-de-sac, pelvis, serosa, uterus, and ovaries Nodules in pelvis and mesentery Papillary excrescences (both ovaries) Pelvic nodules Tumor nodules 0.5-1.0 cm Numerous papillary growths in omentum. Normal ovaries Disseminated tumor pelvis, serosal surface of uterus, and ovaries. Pelvic nodules Id 29 F Left pelvic mass Papillary tumor nodules, pelvis, and ovarian serosa 17 25 F Ascites and suspicious Studding of serosal surface left pelvic mass . of peritoneum with plaques 18 31 F Dyspareunia, spotting, Left ovarian mass (benign ovarian cyst cystic teratoma) numerous nodules 0.7 1.5 cm omentum 19 48 M Incidental finding during Papillary nodule 0.5 cm hernia operation 20 54 M Incidental finding during Papillary nodules on serosa abdominal aortic of large bowel and aneurysm resection numerous mesenteric implants 21 34 M Ascites and weight loss Nodules omentum 22 75 M Incidental finding during Patchy nodules surgery for aortic aneurysm WDPMP: well-differentiated papillary mesothelioma of the peritoneum. Nit Nil Nil Nil Nil Left oophorectomy TAH 4 BSD Omentectomy TAH 4 BSO TAH 4 BSO TAH 4 BSO for adenomyosis Radiotherapy (abdomen and pelvis) Radiotherapy and intraperitoneal chemotherapy (thiotepa) TAH 4 BSO Chemotherapy for associated endometrioid ovarian cancer Radiotherapy (cobalt) TAH 4 BSO omentectomy, radiotherapy, chemotherapy Radiotherapy and chemotherapy Left oophorectomy Nit Nil Nil Nit omentum Follow-up 14 yr, alive and well Died, 29 yr later, of carcinoma ofthe pancreas Multiple nodules of WDPMP on peritoneum at autopsy 1 yr, alive and well 7 yr, alive and well Continued to have ascites. Died 7 yr later ofaplastic anemia (?) ' 5 yr, alive and well Recent case . Recent case 2 yr, alive and well Persistence of disease with .probable increased bulk 8 jt, alive and well N/A N/A 6 yr, alive and well 4 yr, alive and well Persistence of tumor nodules (found during surgery for ventral hernia) 2 yr, alive and well Died 6 weeks after surgery Died 7 yr later, after episodes of intestinal obstruction No autopsy Died 2 yr later Developed radiation enteritis i yr, alive and well J yr, alive and well 8 yr, alive and well. 1 yr, alive and well Persistence of disease 294 Cancer Januaiy 15 1990 Fig. I. WDPMP showing coarse papillae covered by cuboidal ceils. FIg. 3. WDPMP in which the tumor cells form branching cords tumor nodules elsewhere in the abdomen. In other in stances, the ovaries were said to be normal grossly (five cases) or cystic (one case), or their status was not men tioned (six cases). The remaining two female patients had masses in the ovarian region. In one of these patients, the mass was an ovarian endometrioid carcinoma; in the other patient, it was a benign cystic teratoma (Patients 15 and 15), Microscopic Findings There was some variation in the histologic appearances. All had a well-developed papillary architecture in at least some areas, and sometimes the papillae were coarse (Fig. I). A tubulopapillary pattern also was prominent in some tumors. The papillae and tubules in these areas were often lined by a single layer of relatively uniform cuboidal or flattened epithelium (Fig. 2). Also, branching cords of tu mor cells were sometimes seen (Fig. 3). Several tumors showed extensive fibrosis and this was associated with ir regularity ofthe glandular elements in places (Fig. 4). More solid areas oftumor cells were seen in several tumors (Fig. ^ 5). In two cases, scattered multinucleated giant cells wereJ noticed in the stroma. Psammoma bodies were present in five cases (Fig. 6). Mitoses were noticed in only onejl case and occurred in a cellular component of the tumor. J In two instances, isolated tumor nodules showed great J congestion. Tiny "seedling" foci of tumor were occasion-1 ally observed beside larger masses (Fig. 7), In three of the four male patients, the tumor had a j coarse papillary structure. The fourth case had a more | solid growth pattern. PAS or mucicarmine stains were negative in the eight ' cases examined. In the four cases in which immunostain-|| ing was done, the reaction for cytokeratin was positive ! and the reactions for CEA, HMGF-2, and Leu M-l were^ negative. Treatment and Follow-Up Follow-up information for 1 year or more was available'! for most patients (Table 1). Of the 12 patients (Patients? 1t jm 2), frc SOI of to ot as- af & (n al fo a< 0 as d tl h FlG. 2. WDPMP showing a tubulopapillary pattern. The tumor cells are cuboidal and regular. Fig. 4. WDPMP showing extensive fibrosis associated with some ir regularity of the tubuloglandular elements. WDFMP Daya and McCaughey .295 l-/1 -. Fig. 5. WDPMP showing a solid area of tumor. Fig. 7. Seedling foci oftumor that lay close to a large mass. ; 1 through 12) who did not receive any postoperative adj juvant treatment, two had died. In the first patient (Patient 2), who has been reported previously,2 death occurred . from carcinoma of the pancreas 29 years after the mesothelial tumor was first recognized. At autopsy, nodutes of peritoneal tumor, similar in microscopic appearance to those seen in the biopsy specimen 29 years earlier, were observed. The second patient (Patient 5) continued to have ascites and died 7 years after diagnosis, apparently of aplastic anemia. Six of the ten remaining patients in this group have been observed for 1 to 14 years after surgery (mean length of follow-up, 6.2 years). All six patients are alive and well. Follow-up information was not available for two patients and two others were of recent origin. Of the six female patients who received postoperative adjuvant therapy (Patients 13 through 18), three have died. One of these patients (Patient 16) died 6 weeks after di agnosis. Another patient (Patient 18) died 2 years after diagnosis and was thought to have radiation enteritis. The third patient (Patient 17) died 7 years after diagnosis. She had been treated intensively with radiation and chemo- therapy, intestinal obstruction developed in the later stages of her illness. Autopsies were not performed in any of these cases and the contribution of tumor to death is un certain from the available information. Ofthe three treated patients who are alive, one is free of clinical disease 6 . years after surgery (Patient 13). The second patient (Pa tient 14) is alive and well 4 years after diagnosis, although residual tumor has been found in tissue removed from a ventral hernia. The third patient (Patient 15) is well 2 years after diagnosis. At the time of the diagnosis of me- sothelial tumor this patient also was found to have an endometrioid ovarian cancer and subsequently received chemotherapy for this cancer. None of the four male patients has received adjuvant therapy. All are alive and well from 1 to 18 years after surgery (Patients 19 through 22). / Discussion Although mesotheliomas are often thought ofas highly aggressive neoplasms, it is important to remember that one common form, the adenomatoid tumor, is benign. Two other forms, WDPMP and multicystic mesotheli oma,1 are either benign or of no more than low-grade malignant potential. The localized fibrous mesothelioma also is benign in most cases.5 From the gross standpoint, the common presenting sign of multiple peritoneal nodules in WDPMP may lead to confusion with peritoneal carcinomatosis. Pathologically, however, the uniformity of the tumor cells in WDPMP, together with the absence of the nuclear features of ma lignancy and the absence of multilayering of the epithe lium in papillary areas, should usually distinguish it from primary or secondary papillary carcinoma. Confusion with carcinoma is more likely in those uncommon cases of WDPMP in which there is some irregularity of the tubulopapillary elements associated with fibrosis. In such situations, an examination of the nonfibrotic areas of the i 296 Cancer January 15 1990 Voi.65 tumor should indicate the correct diagnosis. Another ma jor .source of diagnostic confusion is the occasional ex ample of diffuse peritoneal malignant mesothelioma where well-differentiated papillary elements are promi nent. In cases of the latter type that we have seen, the tumor masses were bulkier than in WDPMP and adequate histologic sampling showed obvious cancerous areas. When, the lesions of WDPMP are small, the possibility that they represent hyperplasia rather than neoplasia may come under consideration. However, the papillary nature of the lesion, the absence of any reactive changes in ad jacent serosal surfaces, and the absence of antecedent dis ease or surgery make this improbable. Papillary changes may occur in reactive mesothelial hyperplasia2'11"13 but are rarely conspicuous. The occurrence of WDPMP in men is rare. Only three cases appear to have been described in the English liter ature; one was located in the tunica vaginalis,one in the epicardium,16 and one in the pleura,17 In three of our four male patients, the peritoneal tumor was an incidental / finding during abdominal surgery for other purposes. The fourth patient {Patient 21) had ascites and weight loss. At laparotomy, nodules were noticed in the omentum. Three of the men were alive and well 1 year after surgery; the fourth-was well after 8 years. The picture that emerges from the current study of WDPMP is that of a predominantly benign tumor. In occasional cases, however, it is possible that the tumor may behave like a low-grade cancer. Two patients in our series (Patients 17 and 18) died 2 and 7 years after diag nosis under circumstances (radiation enteritis in one case and intestinal obstruction in the other) that made it dif ficult for us to distinguish between the effects of adjuvant therapy and the effects of the tumor. One patient (Patient 5) had continuing ascites and died with query aplastic anemia after 7 years. In another patient (Patient 9) there was evidence that the disease had increased in bulk 1 year after initial surgery. Unfortunately, the quality of follow up information in referred cases, which constituted our material, varies greatly. The need for long-term follow up studies is obvious. In. the meantime, we believe that the available evidencejustifies withholding adjuvant ther apy from patients with WDPMP unless there is a clear indication that the tumor is progressing. Until further information emerges concerning the long term behavior of WDPMP, the designation of well-dif ferentiated seems more appropriate than that of benign. Currently, there is no indication of the cause of WDPMP. In three of our patients, there was a history of i possible exposure to asbestos; however, as two of these ` patients were sisters, a familial influence also may have . ` been involved. Evidence of familial clusteriqg has been j occasionally reported in cases of malignant mesotheli- ; oma.I3 M The female predominance for WDPMP, its fine- * quent occurrence in younger women, its peritoneal lo- ; calization, and its indolent nature are all features that it ; shares with multicystic mesothelioma. There is no evi- ; dence that multicystic mesothelioma is related to as- j bestos.1 ; MA REFERENCES 1. Weiss SW,.Tavassoii FA. Multicystic mesothelioma: An analysis of pathologic findings and biologic behavior in 37 cases. Am J Surg Pathol 1988; 12:737-746. 2. Foyle A, Al-Jabi M, McOaughey WTE. Papillary peritoneal tumors in women. Am J Surg Paiho! 1981; 5:241-249. 3. Goepel JR. Benign papillary mesothelioma of peritoneum. His- lopaihology 1981; 5:21-30. 4. McCaughey WTE. Papillary peritoneal neoplasms in females. In: Sommers SC, Rosen PP, Fechner RE, eds. Pathology Annual, Part 2. ! : New York: Appleton-Cenlury-Orofts, 1985; 387-404. 5. McCaughey WTE, Kannerstein M, Cburg J. Tumors and pseu- dotumore of the serous membranes. In: Atlas ofTumor Pathology, Series 2, Fascicle 20. Washington, DC: Armed Forces Institute of Pathology, ]9S5. f 6. Rhind JA, Wright CJE. Mesothelioma of the peritoneum. Br J Surg 1949; 35:359-363. 7. Wells AH. Papillomatosis peritonei, AmJPalhoi 1935; 11:1011 1013. 8. Parmley TH, WoodiufFJD. The ovarian mesothelioma. AmJ Obstet Gynecol 1974; 120:234-240. 9. Blaustein A. Surface (germinal) epithelium and related ovarian 7 neoplasms. In: Sommers SC, Rosen PP, eds. Pathology Annual, Part 1. New York: Appleton-Century-Crofts, 1981; 247-294. 10. Ryan GB, Grobety J, Majno G. Mesothelial injury and recovery. AmJ Pathol 1973; 71:93-112. 11. Rosai J, Dehner LP. Nodular mesothelial hyperplasia in hernia sacs; A benign condition simulating a neoplastic process. Cancer 1975; 35:165-175. 12. McCaughey WTE, Al-Jabi M. Differentiation ofserosal hyperplasia and neoplasia in biopsies. In: Sommers SC, Rosen PP, Fechner RE, eds. ' Pathology Annual, Part 1. New York: Appleton-Century-Crofts, 1986; 271-294. ... 13. Risberg B, Nickels J, Wagermark J. Familial clustering ofmalig nant mesothelioma. Cancer 1980; 45:2422-2427. 14. Lynch HT, Katz D, Markivicka SE. Familial-mesothelioma: Re view and family study. Cancer Genet Cytogenet 1985; 15:25-35. 15. Barbera V, Rubino M. Papillary mesothelioma of the tunica va ginalis. Cancer 1957; 10:183-189. . 16. Larsen TE. Serosal papilloma ofthe epicardium, Arch Pathol 1974; 97:271-272, 17. Yesner R, Hurwitz A. Localized pleural mesothelioma ofepithelial type. J Thorac Surg 1953; 26:325-329. E sa ah in in Pi IE a tl ct P ii It it S s t < 1