Serous Surface Carcinoma of the Peritoneum: A Clinicopathologic Study of 22 Cases LUAN D. TRUONG, MD, MAURIZIO L. MACCATO, MD, HAZEL AWALT, MD, PHILIP T. CAGLE, MD, MARY R. SCHWARTZ MD, AND AIAN L. KAPLAN, MD troversial. These considerations are the focus of the current study which includes 22 new cases of SSC.
Serous surface carcinoma (SSC) of the peritoneum is defined as a primary tumor histologically indistinguishable from serous carcinoma of the ovary, diffusely involving the peritoneal surface but sparing or only superficially invading the ovaries. In this study of 22 cases of SSC, it was found that the main clinical manifestations of SSC were abdominal pain and enlargement. In most cases, SSC evenly involved the entire mesothelial surface but rarely was predominant in or even limited to the pelvis. It frequently invaded the submesothelium, but deep invasion into abdominal and pelvic organs or local metastasis was rare, and distant metastasis was not seen at presentation. Microscopically, SSC was a high-grade tumor frequently showing high mitotic rate, psammomas bodies, and necrosis. The tumor was usually contiguous with hyperplastic mesotbelium on either ovarian surface or other locations. Tumor cells in all cases except one showed cytoplasmic or surface neutral or acidic mucin or both. Tumor cells stained positive for keratin (100% of cases), epithelial membrane antigen (lOO%), Leu-Ml (45%), B72.3 (85%), vimentin (35%), and carcinoembryonic antigen (25%). Electron microscopic studies of six cases showed epithelial differentiation in each. Seven patients (32%) were alive with no clinical disease at 3 to 31 months, one patient (4%) was alive with extensive local disease at 24 months, 11 patients (50%) died almost exclusively of local recurrence at 1 to 70 months, and three patients (14%) died of operative complications. It is concluded that SSC arises from peritoneal mesothelium but has epithelial phenotype. It can be morphologically differentiated from other conditions with similar laparotomy findings, such as malignant mesothelioma, benign papillary mesothelioma, cystic mesothelioma, and benign or borderline peritoneal serous tumors. The prognosis of SSC is poor, and most patients die of uncontrollable local disease. HUM PATHOL 21:99-l 10. 0 1990 by W.B. Saunders Company.
MATERIALS AND METHODS The 22 cases of SSC were identified from the files of the Departments of Pathology at the Methodist Hospital and St. Luke’s Episcopal Hospital (Houston, TX) from 1968 to 1988, and from the consultation file of one of us (A.K.). Glass slides of every case (12 to 42/ease) were examined and morphologic features were tabulated. Sections from selected blocks of 20 cases were stained by periodic acid-Schiff (PAS) with and without diastase digestion, by alcian blue at pH 2.5 with or without hyaluronidase digestion, and by mucicarmine stains. Additional sections from the same blocks were also stained by the avidinbiotin-peroxidase technique for the antigens listed in Table 1. Electron microscopic studies were done on six tumors. To assess the histogenesis of SSC, the histochemical and immunohistochemical features of SSC were compared with those of ovarian serous carcinoma (11 cases), surface epithelium of the ovary (11 cases), and reactive mesothelium of the epithelioid cell type (nine cases) and the spindle cell type (14 cases). Clinical features were tabulated for each case and correlated with morphologic findings. Each case of SSC was staged and graded according to the systems proposed by the World Health Organization and the Federation International de Gynecologie et Obstetrique.
RESULTS Clinical Features
Serous surface carcinoma (SSC) of the peritoneum is defined as a primary tumor histologically indistinguishable from serous carcinoma of the ovary, diffusely involving the peritoneal surface but sparing or only superficially invading the ovaries. Although approximately 124 cases of SSC have been described, mostly in single-case reports,le5 small series6-r6 or abstracts17s18 under a variety of names including “peritoneal papillary serous carcinoma,“10-13 “multiple focal extraovarian serous carcinoma,“(j “peritonial mesothelioma,“1g~20 or “serous surface papillary features, carcinoma,“g*‘6,‘4 the immunohistochemical clinical behavior, and histogenesis of SSC remain con-
Table 1 presents the data for the clinical features. All patients were women ranging in age from 25 to 74 years (mean, 56 years). Although most patients presented with abdominal enlargement and/or pain, a palpable mass or masses were noted in only five (22%). Radiologic studies, including computed tomography (CT) scans done in 14 cases, were usually noncontributory. Preoperative, postoperative, and intraoperative evaluation showed peritoneal tumors but no other primary tumors. Cytologic examination of ascitic fluid done in 13 cases always showed malignant cells. Most patients were treated by various combinations of hysterectomy, oophorectomy, omentectomy, biopsy of the peritoneal tumor implants, and tumor debulking. In three patients, hysterectomy and bilateral or unilateral oophorectomy had been performed previously for various benign diseases (Table 1). With the exception of two patients who died of operative complications, all patients received postoperative chemotherapy. Two patients showed persistence of original disease; the 18 other patients experienced a decrease of tumor bulk as ev-
From the Departments of Pathology and Obstetrics & Gynecology, The Methodist Hospital, St Luke’s Episcopal Hospital, and Baylor College of Medicine, Houston, TX. Accepted for publication July 5, 1989. Key words: serous surface carcinoma, peritoneum.
Address correspondence and reprint requests to Luan D. Truong, MD, Baylor College of Medicine, Department of Pathology, One Baylor Plaza, Houston, TX 77030. 0 1990 by W.B. Saunders Company. 0046-8177/90/2101-0014$5.00/O
99
HUMAN PATHOLOGY
TABLE 1. Age
Serous Surface Papillary Carcinoma of the Peritoneum: Clinical Findings in 22 Cases
Clinical Manifestations
Duration Stages (wk)
Case
!!Z/
1
50/F
2
60/F
3
54/F
4
54/F
5
42/F
6
64/F
Abd swelling and low back pain
4
7
64/F
3
8
25/F
9
73/F
10
64/F
11
61/F
12
51/F
13
67/F
14
45/F
Abd pain and swelling, anorexia Abd pain, dyspareunia Abd pain and swelling, diarrhea Melenotic stool, dizziness Abd pain and swelling Abd pain and swelling Abd pain and swelling, weight loss Abd pain and mass
15
64/F
16
63/F
17
35/F
18
65/F
19
74/F
20
59/F
21
55/F
22
59/F
Volume 21, No. 1 [January 1990)
Abd pain and swelling, N&V Abd pain and swelling Abd pain and swelling Abd pain and swelling Abd pain
Abd pain and swelling, intestinal obstruction Abd pain and swelling, retrosternal pain, N&V Progressive abd discomfort
2 2 10 3 16
4 3 Few d 12 12 6 5
8
3
16
Recurrence after Chemotherapy (mo)
Treatment
Metastasis (mo)
Outcome (mo)
BSO, om: sigmoidectomy Om, colostomy
No§
No
Alive/well (4)
NA
No
Om, jejunectomy, debulking* TAHIBSO, bx, chemotherapy BSO, om, bx, chemotherapy BSO, om, debulkings, chemotherapy TAHIBSO, om, chemotherapy Om, bx, chemotherapy BSO, om, bx, chemotherapy BSO, bx, colectomy
No
No
No Yes, CT scan (6)
Pleura, liver and mediastinum (3) Liver (6)
Intraoperative death Died of pulmonary embolism (2) DOD (9)
No
No
Alive/well (6)
No
No
Alive/well (4)
No
No
Alive/well (4)
No
No
Alive/well (3 1)
Yes, CT scan (24)
No
No
No
Alive with disease (24) Alive/well (11)
Yes, 2nd operation (49) Yes, 2nd operation (21) Persistent disease
No
DOD (70)
No
DOD (24)
Retroperitoneal lymph nodes (at presentation) No
DOD (5)
No
DOD (1)
Yes, 2nd operation (9)
No
DOD (20)
Yes, 2nd operation (12)
No
DOD (14)
Died of postoperative hemorrhage (2 d) Alive with disease
TAH/BSO, om, chemotherapy BSO, om, chemotherapy BSO, bx, chemotherapy Om, colostomy, chemotherapyg Pelvic exenteration, om, chemotherapy BSO, om, sigmoidectomy, debulking, chemotherapy Vaginal hysterectomy, BSO, om, appendectomy, debulking, chemotherapy BSO, appendectomy, bx, chemotherapy
Yes, 2nd operation
DOD (14)
DOD (15)
(12) Persistent
disease
Weight loss, abd pain (24 wk), malignant ascites and abd mass (2 wk) Intermittent severe abd pain
24
12
BSO, om
NA
No
Abd pain and swelling Abd pain and swelling, N&V Abd pain and swelling
12
TAHIBSO, om, bx, chemotherapy Om, chemotherapyt
Yes, 2nd operation (8) Yes, 2nd operation (23) Yes, 2nd operation
Liver (20)
(6) DOD (24)
No
DOD (19)
1 6
BSO, om, appendectomy, debulking, chemotherapy
(9) Yes, 3rd operation (18)
Abbreviations: abd, abdominal; BSO, bilateral salpingo-oophorectomy; bx, biopsy of tumor implants; DOD, died of disease; N&V, nausea and vomiting; om, omentectomy; NA, not applicable; TAH, total abdominal hysterectomy. * TAH/BSO 14 years previously for endometriosis and mature cystic teratoma of the ovaries. t TAH/BSO 3 years previously for leiomyomas and endometrial adenomatous hyperplasia with normal ovaries and tubes. $ TAH/LSO 16 years previously for an ovarian “cyst.” I No recurrence is defined as absence of clinical abdominal manifestations and negative abdominal imaging studies or absence of tumor at second-look operation.
SEROUS SURFACE CARCINOMA (Truong et al) 5 previously removed:
all normal 5 not removed (3 with tumor on surface) ~ 34 removed ~
gross:
23 wllh tumor on surlace
microscopic: 20 with t~rnor on sudace (12 01 whtch have svperhcial (less lhan 3 mm) invasion] 5 previously removed:
all normal
10 norremoved
FIGURE 1. Extent of tumor involving ovaries, fallopian tubes, and uterus.
k
39 remanned
Serous surface carcinoma (SSC) of the peritoneum is defined as a primary tumor histologically indistinguishable from serous carcinoma of the ovary, diffusely involving the peritoneal surface but sparing or only superficially invading the ovaries. In this study of 22 cases of SSC, it was found that the main clinical manifestations of SSC were abdominal pain and enlargement. In most cases, SSC evenly involved the entire mesothelial surface but rarely was predominant in or even limited to the pelvis. It frequently invaded the submesothelium, but deep invasion into abdominal and pelvic organs or local metastasis was rare, and distant metastasis was not seen at presentation. Microscopically, SSC was a high-grade tumor frequently showing high mitotic rate, psammomas bodies, and necrosis. The tumor was usually contiguous with hyperplastic mesotbelium on either ovarian surface or other locations. Tumor cells in all cases except one showed cytoplasmic or surface neutral or acidic mucin or both. Tumor cells stained positive for keratin (100% of cases), epithelial membrane antigen (lOO%), Leu-Ml (45%), B72.3 (85%), vimentin (35%), and carcinoembryonic antigen (25%). Electron microscopic studies of six cases showed epithelial differentiation in each. Seven patients (32%) were alive with no clinical disease at 3 to 31 months, one patient (4%) was alive with extensive local disease at 24 months, 11 patients (50%) died almost exclusively of local recurrence at 1 to 70 months, and three patients (14%) died of operative complications. It is concluded that SSC arises from peritoneal mesothelium but has epithelial phenotype. It can be morphologically differentiated from other conditions with similar laparotomy findings, such as malignant mesothelioma, benign papillary mesothelioma, cystic mesothelioma, and benign or borderline peritoneal serous tumors. The prognosis of SSC is poor, and most patients die of uncontrollable local disease. HUM PATHOL 21:99-l 10. 0 1990 by W.B. Saunders Company.
MATERIALS AND METHODS The 22 cases of SSC were identified from the files of the Departments of Pathology at the Methodist Hospital and St. Luke’s Episcopal Hospital (Houston, TX) from 1968 to 1988, and from the consultation file of one of us (A.K.). Glass slides of every case (12 to 42/ease) were examined and morphologic features were tabulated. Sections from selected blocks of 20 cases were stained by periodic acid-Schiff (PAS) with and without diastase digestion, by alcian blue at pH 2.5 with or without hyaluronidase digestion, and by mucicarmine stains. Additional sections from the same blocks were also stained by the avidinbiotin-peroxidase technique for the antigens listed in Table 1. Electron microscopic studies were done on six tumors. To assess the histogenesis of SSC, the histochemical and immunohistochemical features of SSC were compared with those of ovarian serous carcinoma (11 cases), surface epithelium of the ovary (11 cases), and reactive mesothelium of the epithelioid cell type (nine cases) and the spindle cell type (14 cases). Clinical features were tabulated for each case and correlated with morphologic findings. Each case of SSC was staged and graded according to the systems proposed by the World Health Organization and the Federation International de Gynecologie et Obstetrique.
RESULTS Clinical Features
Serous surface carcinoma (SSC) of the peritoneum is defined as a primary tumor histologically indistinguishable from serous carcinoma of the ovary, diffusely involving the peritoneal surface but sparing or only superficially invading the ovaries. Although approximately 124 cases of SSC have been described, mostly in single-case reports,le5 small series6-r6 or abstracts17s18 under a variety of names including “peritoneal papillary serous carcinoma,“10-13 “multiple focal extraovarian serous carcinoma,“(j “peritonial mesothelioma,“1g~20 or “serous surface papillary features, carcinoma,“g*‘6,‘4 the immunohistochemical clinical behavior, and histogenesis of SSC remain con-
Table 1 presents the data for the clinical features. All patients were women ranging in age from 25 to 74 years (mean, 56 years). Although most patients presented with abdominal enlargement and/or pain, a palpable mass or masses were noted in only five (22%). Radiologic studies, including computed tomography (CT) scans done in 14 cases, were usually noncontributory. Preoperative, postoperative, and intraoperative evaluation showed peritoneal tumors but no other primary tumors. Cytologic examination of ascitic fluid done in 13 cases always showed malignant cells. Most patients were treated by various combinations of hysterectomy, oophorectomy, omentectomy, biopsy of the peritoneal tumor implants, and tumor debulking. In three patients, hysterectomy and bilateral or unilateral oophorectomy had been performed previously for various benign diseases (Table 1). With the exception of two patients who died of operative complications, all patients received postoperative chemotherapy. Two patients showed persistence of original disease; the 18 other patients experienced a decrease of tumor bulk as ev-
From the Departments of Pathology and Obstetrics & Gynecology, The Methodist Hospital, St Luke’s Episcopal Hospital, and Baylor College of Medicine, Houston, TX. Accepted for publication July 5, 1989. Key words: serous surface carcinoma, peritoneum.
Address correspondence and reprint requests to Luan D. Truong, MD, Baylor College of Medicine, Department of Pathology, One Baylor Plaza, Houston, TX 77030. 0 1990 by W.B. Saunders Company. 0046-8177/90/2101-0014$5.00/O
99
HUMAN PATHOLOGY
TABLE 1. Age
Serous Surface Papillary Carcinoma of the Peritoneum: Clinical Findings in 22 Cases
Clinical Manifestations
Duration Stages (wk)
Case
!!Z/
1
50/F
2
60/F
3
54/F
4
54/F
5
42/F
6
64/F
Abd swelling and low back pain
4
7
64/F
3
8
25/F
9
73/F
10
64/F
11
61/F
12
51/F
13
67/F
14
45/F
Abd pain and swelling, anorexia Abd pain, dyspareunia Abd pain and swelling, diarrhea Melenotic stool, dizziness Abd pain and swelling Abd pain and swelling Abd pain and swelling, weight loss Abd pain and mass
15
64/F
16
63/F
17
35/F
18
65/F
19
74/F
20
59/F
21
55/F
22
59/F
Volume 21, No. 1 [January 1990)
Abd pain and swelling, N&V Abd pain and swelling Abd pain and swelling Abd pain and swelling Abd pain
Abd pain and swelling, intestinal obstruction Abd pain and swelling, retrosternal pain, N&V Progressive abd discomfort
2 2 10 3 16
4 3 Few d 12 12 6 5
8
3
16
Recurrence after Chemotherapy (mo)
Treatment
Metastasis (mo)
Outcome (mo)
BSO, om: sigmoidectomy Om, colostomy
No§
No
Alive/well (4)
NA
No
Om, jejunectomy, debulking* TAHIBSO, bx, chemotherapy BSO, om, bx, chemotherapy BSO, om, debulkings, chemotherapy TAHIBSO, om, chemotherapy Om, bx, chemotherapy BSO, om, bx, chemotherapy BSO, bx, colectomy
No
No
No Yes, CT scan (6)
Pleura, liver and mediastinum (3) Liver (6)
Intraoperative death Died of pulmonary embolism (2) DOD (9)
No
No
Alive/well (6)
No
No
Alive/well (4)
No
No
Alive/well (4)
No
No
Alive/well (3 1)
Yes, CT scan (24)
No
No
No
Alive with disease (24) Alive/well (11)
Yes, 2nd operation (49) Yes, 2nd operation (21) Persistent disease
No
DOD (70)
No
DOD (24)
Retroperitoneal lymph nodes (at presentation) No
DOD (5)
No
DOD (1)
Yes, 2nd operation (9)
No
DOD (20)
Yes, 2nd operation (12)
No
DOD (14)
Died of postoperative hemorrhage (2 d) Alive with disease
TAH/BSO, om, chemotherapy BSO, om, chemotherapy BSO, bx, chemotherapy Om, colostomy, chemotherapyg Pelvic exenteration, om, chemotherapy BSO, om, sigmoidectomy, debulking, chemotherapy Vaginal hysterectomy, BSO, om, appendectomy, debulking, chemotherapy BSO, appendectomy, bx, chemotherapy
Yes, 2nd operation
DOD (14)
DOD (15)
(12) Persistent
disease
Weight loss, abd pain (24 wk), malignant ascites and abd mass (2 wk) Intermittent severe abd pain
24
12
BSO, om
NA
No
Abd pain and swelling Abd pain and swelling, N&V Abd pain and swelling
12
TAHIBSO, om, bx, chemotherapy Om, chemotherapyt
Yes, 2nd operation (8) Yes, 2nd operation (23) Yes, 2nd operation
Liver (20)
(6) DOD (24)
No
DOD (19)
1 6
BSO, om, appendectomy, debulking, chemotherapy
(9) Yes, 3rd operation (18)
Abbreviations: abd, abdominal; BSO, bilateral salpingo-oophorectomy; bx, biopsy of tumor implants; DOD, died of disease; N&V, nausea and vomiting; om, omentectomy; NA, not applicable; TAH, total abdominal hysterectomy. * TAH/BSO 14 years previously for endometriosis and mature cystic teratoma of the ovaries. t TAH/BSO 3 years previously for leiomyomas and endometrial adenomatous hyperplasia with normal ovaries and tubes. $ TAH/LSO 16 years previously for an ovarian “cyst.” I No recurrence is defined as absence of clinical abdominal manifestations and negative abdominal imaging studies or absence of tumor at second-look operation.
SEROUS SURFACE CARCINOMA (Truong et al) 5 previously removed:
all normal 5 not removed (3 with tumor on surface) ~ 34 removed ~
gross:
23 wllh tumor on surlace
microscopic: 20 with t~rnor on sudace (12 01 whtch have svperhcial (less lhan 3 mm) invasion] 5 previously removed:
all normal
10 norremoved
FIGURE 1. Extent of tumor involving ovaries, fallopian tubes, and uterus.
k
39 remanned
