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Background
This condition is a cancer characterized by extensive spread of a mucin-secreting neoplasm along the peritoneal surfaces. Although usually diffuse, rare cases may be limited to a solitary site such as hernia sac. Histopathological examination of the mucin may reveal mucin only, mucin with inflammatory cells, mucin which dissects the surrounding collage, and mucin with neoplastic cells. These neoplastic cells are usually well-differentiated mucin secreting columnar cells.
This diagnosis commits the pathologist to search for a primary tumor. The most common site is a low grade mucinous tumor of the appendix. Other sites include ovary and pancreas. Most cases of cystic ovarian mucinous tumors associated with pseudomyxoma peritonei are associated with metastases from an appendiceal tumor.
OUTLINE
CLINICAL VARIANTS CHARACTERIZATION Pseudomyxoma peritonei: a review of 62 cases.
van Ruth S, Acherman YI, van de Vijver MJ, Hart AA, Verwaal VJ, Zoetmulder FA.
Department of Surgical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Amsterdam, The Netherlands.
Eur J Surg Oncol. 2003 Oct;29(8):682-8. Abstract quote
AIM: Pseudomyxoma peritonei (PMP) is a rare disease characterized by the abundance of mucus in the abdomen without extra-peritoneal growth.
METHODS: Our patients with PMP have been treated with cytoreduction and hyperthermic intraperitoneal chemotherapy since 1996. The clinical and histopathological features of PMP and the relation of these features with disease-free interval and survival were assessed.
RESULTS: Sixty-two patients with PMP (24 M/38 F) were studied. Adenomatous mucosal changes were present in 31 patients. In females, the ovaries were normal in 5 patients and pseudomyxoma ovarii was present in 20 patients. Patients with minimal atypia and with 1% focal proliferation or less (n=38) had a better survival (p=0.0008) than those with more focal proliferation (n=14).
CONCLUSION: In most patients with PMP the appendix is affected; in females the ovaries are usually also involved. Focal proliferation appears to be a prognostic factor.
HISTOLOGICAL TYPES CHARACTERIZATION General VARIANTS Adenomucinosis Adenomucinosis was characterized by multifocal mucinous tumors adherent to but not invading into visceral and parietal peritoneal surfaces.
Microscopically, the peritoneal lesions contained scant histologically benign mucinous epithelium within abundant extracellular mucin
An intense hyalinizing fibrotic reaction that separated pools of mucin
Mucinous adenocarcinoma Mucinous adenocarcinoma was characterized by invasive peritoneal lesions composed of abundant epithelium with glandular or signet-ring cell morphology with sufficient architectural complexity and cytological atypia to warrant a diagnosis of mucinous adenocarcinoma
Mucinous adenocarcinomas were further separated into three grades:
Well-differentiated
Moderately differentiated
Poorly differentiated adenocarcinomaHybrid Hybrid appendiceal mucinous tumors included foci of intermediate type and diffuse peritoneal adenomucinosis histology present within the same clinical material
VARIANTS
- Appendiceal mucinous tumors and pseudomyxoma peritonei: histologic features, diagnostic problems, and proposed classification.
Pai RK, Longacre TA.
From the Department of Pathology, Stanford University School of Medicine, Stanford, CA
Adv Anat Pathol. 2005 Nov;12(6):291-311. Abstract quote
Pseudomyxoma peritonei is an overused and underspecified condition that has garnered much attention in the historic literature. In recent years, this condition has been convincingly linked to appendiceal mucinous neoplasms, yet there has been insufficient attention to the histologic characteristics, classification, and differential diagnostic considerations of these neoplasms when encountered by the surgical pathologist.
This review provides a coherent approach to the diagnosis and classification of appendiceal mucinous tumors and the peritoneal implants associated with the pseudomyxoma peritonei syndrome with emphasis on differential diagnostic considerations and recommendations for the final pathology report.Gelatinous Ascites: A Cytohistologic Study of Pseudomyxoma Peritonei in 67 Patients
Stephanie L. Jackson, M.D., Ronald A. Fleming, PhD., Brian W. Loggie, M.D. and Kim R. Geisinger, M.D.
Department of Pathology (SLJKRG), Wake Forest University Baptist Medical Center, Winston-Salem, North Carolina; Clinical Research Program (RAF), Glaxo Wellcome, Inc., Research Triangle Park, North Carolina; and University of Texas Southwestern Medical Center (BWL), Moncrief Cancer Center, Fort Worth, Texas
Mod Pathol 2001;14:664-671 Abstract quote
Pseudomyxoma peritonei (PMP) is a rare condition characterized by gelatinous ascites. Although the histologic attributes of PMP have been well studied, the cytologic features remain ill defined. METHODS:
We reviewed the peritoneal washings (PW) in 67 patients with PMP to identify cytomorphologic features useful in classifying cases as either disseminated peritoneal adenomucinosis (DPAM) or peritoneal mucinous carcinomatosis (PMCA).
Histologic specimens were correlated with the cytologic diagnoses. Correlation between cytologic diagnosis and patient outcome was investigated. RESULTS: Neoplastic epithelial cells were identified in 63 of 67 PW (94%). Concordance with the histologic diagnosis was obtained in 61 of 63 cases. Of these 36.5% were cytologically classified as DPAM with primary appendiceal neoplasms in 19 cases. Thirty-four of 63 cases (53.9%) were cytologically diagnosed as PMCA based on PW cytology. Most were of appendiceal or colonic origin. Four cases displayed cytologic features of both DPAM and PMCA. Two discordant cases each with a cytologic diagnosis of PMCA had an appendiceal adenoma. Acellular mucin alone was identified in the PW in four cases. Analysis of follow-up data revealed that cases diagnosed as DPAM had a better prognosis than those diagnosed as PMCA.
CONCLUSIONS: Cytomorphologic features of epithelial cells in PW material can accurately categorize cases of PMP as either DPAM or PMCA. Furthermore, this categorization appears to have important prognostic implications.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSTIC FACTORS Histopathologic Analysis in 46 Patients with Pseudomyxoma Peritonei Syndrome: Failure versus Success with a Second-Look Operation
Hui Yan, etal.
Mod Pathol 2001;14:164-171 Abstract quote
Pseudomyxoma peritonei syndrome is a disease characterized by mucinous ascites and mucinous tumor disseminated on peritoneal surfaces; the disease almost always originates from a perforated appendiceal epithelial tumor. Histopathologic assessment of aggressive versus noninvasive character of the mucinous tumor has been shown to have an impact on survival in patients treated with cytoreductive surgery and intraperitoneal chemotherapy.
Out of a database of 312 patients having a complete cytoreduction for pseudomyxoma peritonei syndrome, 46 patients (24 male and 22 female) had at least one second-look surgery. Before this review, all 46 of these patients were clinically uniformly categorized with a diagnosis of pseudomyxoma peritonei. Using the criteria described by Ronnett and colleagues, all specimens from the multiple surgical procedures performed on these patients were reviewed and reclassified as disseminated peritoneal adenomucinosis (adenomucinosis), adenomucinosis/mucinous adenocarcinoma (hybrid), or mucinous adenocarcinoma.
The review was performed in a blinded fashion by a single pathologist (HY). To facilitate a critical evaluation of these histopathologic assessments, the patients were separated into two groups: (1) 19 patients who had a second-look surgery that was unsuccessful in that they went on to die of their disease or in that they currently have disease progression and a limited survival and (2) 27 patients who had a successful second look and currently continue disease free with a minimum 3-year follow-up period.
As a result of this review, 11 of 19 patients with an unsuccessful second look and originally designated pseudomyxoma peritonei were reclassified as hybrid-type malignancy (four patients) or mucinous adenocarcinoma (seven patients). Only two patients were reclassified in the successful second-look group (P = .0005). Transitions from a less aggressive to a more invasive histology from one cytoreduction to the next occurred on 13 occasions in patients whose second-look surgery failed and in one patient with a successful second-look surgery (P < .0001). Seven patients retained a histologic classification of disseminated peritoneal adenomucinosis but went on to die of an aggressive disease process. Clinical assessments suggested that failure of second-look surgery for pseudomyxoma peritonei was associated with a biologically more aggressive disease.
Unsuccessful second-look surgery for patients with a clinical diagnosis of pseudomyxoma peritonei tumor was often related to an inaccurate initial histologic classification of appendiceal mucinous tumor. Also, a transition from less to more aggressive histology was frequently seen in patients dying of this disease. Assessment of tumor histology can predict the outcome if a uniform surgical treatment is used in patients with peritoneal dissemination of mucinous epithelial tumors of the appendix.
Patients with pseudomyxoma peritonei associated with disseminated peritoneal adenomucinosis have a significantly more favorable prognosis than patients with peritoneal mucinous carcinomatosis.
Ronnett BM, Yan H, Kurman RJ, Shmookler BM, Wu L, Sugarbaker PH.
Department of Pathology, The Johns Hopkins Hospital, Baltimore, Maryland 21231, USA.
Cancer 2001 Jul 1;92(1):85-91 Abstract quote
BACKGROUND: Pseudomyxoma peritonei (PMP) is a poorly understood condition characterized by disseminated intraperitoneal mucinous tumors, often with mucinous ascites. The term PMP has been applied historically as a pathologic diagnostic term to both benign and malignant mucinous neoplasms that produce abundant extracellular mucin, resulting in a variable and poorly predictable prognosis. A recent study reported a pathologic classification that separated patients into prognostically distinct groups, but the follow-up was relatively short.
METHODS: Long-term follow-up data were analyzed for a previously reported series of 109 patients with PMP to examine the prognostic utility of a pathologic classification system that divided patients into three groups: disseminated peritoneal adenomucinosis (DPAM), peritoneal mucinous carcinomatosis (PMCA), and peritoneal mucinous carcinomatosis with intermediate or discordant features (PMCA-I/D). Patients whose tumors were classified 25 DPAM (n = 65 patients) had disease that was characterized by histologically bland to low-grade adenomatous mucinous epithelium associated with abundant extracellular mucin and fibrosis, often with an identifiable appendiceal mucinous adenoma that was the source of the peritoneal lesions. Patients whose tumors were classified 25 PMCA (n = 30 patients) had disease that was characterized by peritoneal lesions that displayed the cytologic and architectural features of mucinous carcinoma associated with extracellular mucin, often with an identifiable invasive mucinous adenocarcinoma of the gastrointestinal tract. Patients whose tumors were classified 25 PMCA-I (n = 11 patients) had peritoneal lesions that combined the features of DPAM and PMCA derived from well differentiated mucinous adenocarcinomas associated with adenomas. Patients whose tumors were classified 25 PMCA-D (n = 3 patients) had markedly atypical appendiceal adenomas associated with peritoneal lesions similar to PMCA.
RESULTS: Patients with DPAM had 5-year and 10-year survival rates of 75% and 68%, respectively (mean follow-up, 96 months; median follow-up, 104 months). Patients with PMCA and PMCA-I/D had a significantly worse prognosis, with 5-year and 10-year survival rates, respectively, of 50% and 21% for PMCA-I/D (mean follow-up, 58 months; median follow-up, 51 months) and 14% and 3% for PMCA (mean follow-up, 27 months; median follow-up, 16 months; P = 0.0001).
CONCLUSIONS: The term PMP should be used only as a clinical descriptor for patients who have the syndrome of mucinous ascites accompanied by a characteristic distribution of peritoneal mucinous tumors with the pathologic features of DPAM. DPAM should be used as a pathologic diagnostic term for patients with the bland peritoneal mucinous tumors associated with ruptured appendiceal mucinous adenomas and PMP. These patients should not be diagnosed with carcinoma, because they have disease that is distinct pathologically and prognostically from PMCA.
TREATMENT CHEMOTHERAPY Extensive surgical cytoreduction and intraoperative hyperthermic intraperitoneal chemotherapy in patients with pseudomyxoma peritonei.
Witkamp AJ, de Bree E, Kaag MM, van Slooten GW, van Coevorden F, Zoetmulder FA.
Department of Surgical Oncology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Br J Surg 2001 Mar;88(3):458-63 Abstact quote
BACKGROUND: Pseudomyxoma peritonei remains a fatal disease. However, extensive surgical cytoreduction combined with intraoperative heated intraperitoneal chemotherapy (HIPEC) has recently emerged as a new treatment modality, which might improve survival.
METHODS: Patients underwent treatment if the tumour appeared to be technically resectable on preoperative abdominal computed tomography and there were no distant metastases. After aggressive surgical cytoreduction, HIPEC with the administration of mitomycin C was performed for 90 min. Depending on histological grading, patients received adjuvant 5-fluorouracil and leucovorin therapy.
RESULTS: Forty-six patients were treated. Optimal surgical cytoreduction was obtained in 40 patients. Postoperative surgical complications occurred in 18 patients. Four patients died as a direct result of the treatment. Bone marrow suppression due to mitomycin C toxicity occurred in 22 patients. There was no other major toxicity related to the HIPEC procedure. After a median follow-up of 12 months, 40 patients are alive, eight of whom have proven recurrence. The actuarial survival rate (Kaplan-Meier) at 3 years was 81 per cent.
CONCLUSION: These results confirm that extensive surgery combined with HIPEC is feasible in patients with pseudomyxoma peritonei and that improved long-term survival might be achieved.
Cytoreductive surgery and peri-operative intraperitoneal chemotherapy as a curative approach to pseudomyxoma peritonei syndrome.
Sugarbaker PH.
Washington Cancer Institute, Washington, DC, USA.
Eur J Surg Oncol 2001 Apr;27(3):239-43 Abstract quote
Peritoneal carcinomatosis, regardless of primary tumour type, has always been a lethal condition. Recently special treatments using cytoreductive surgery with peritonectomy procedures combined with peri-operative intraperitoneal chemotherapy have resulted in long-term survival. Pseudomyxoma peritonei may be especially appropriate for these aggressive local regional treatments.
All patients treated prior to 1999 are presented; patients left with gross residual disease after surgery were not given intraperitoneal chemotherapy, but were later treated with intravenous chemotherapy after cytoreduction. The intraperitoneal chemotherapy was given in the peri-operative period, starting with mitomycin C. For patients whose pathology showed adenomucinosis, intraperitoneal chemotherapy was limited to treatment in the operating theatre with heated mitomycin C. Patients with mucinous adenocarcinoma or pseudomyxoma/adenocarcinoma hybrid had, in addition to mitomycin C, 5 consecutive days of intraperitoneal 5-fluorouracil. A complete cytoreduction was defined as tumour nodules <2.5 mm in diameter remaining after surgery. The histopathology categorized the patients as adenomucinosis, intermediate type, or mucinous carcinomatosis. A prior surgical score was used to estimate the extent of previous surgical procedures. The morbidity of treated patients was 27% and the mortality was 2.7%.
In a multivariate analysis, prognostic factors for survival included the completeness of cytoreduction (P<0.0001), the histopathological character of the appendix malignancy (P<0.001) and the extent of previous surgical interventions (P=0.001). Patients with a complete cytoreduction and adenomucinosis by pathology had a 5-year survival of 86%; while hybrid pathology survival at 5 years was 50%. Incomplete cytoreduction had a 5-year survival of 20% and 0% at 10 years. Cytoreductive surgery and peri-operative intraperitoneal chemotherapy is the current standard treatment for selected patients with peritoneal surface spread of appendiceal primary tumours. Similar strategies for other patients with peritoneal surface malignancy such as peritoneal carcinomatosis from colon or gastric cancer, peritoneal sarcomatosis, or peritoneal mesothelioma should be pursued.
INTRAPERITONEAL HYPERTHEMERIC PERFUSION (IPHP)
Peritonectomy and intraperitoneal hyperthermic perfusion (IPHP): a strategy that has confirmed its efficacy in patients with pseudomyxoma peritonei.
Deraco M, Baratti D, Inglese MG, Allaria B, Andreola S, Gavazzi C, Kusamura S.
Department of Surgery, Melanoma and Sarcoma Unit, National Cancer Institute of Milan, Italy.
Ann Surg Oncol. 2004 Apr;11(4):393-8 Abstract quote
BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare disease with a poor prognosis characterized by a complete redistribution of mucin within the peritoneal cavity. The aim of this multicentric study was to evaluate the survival, morbidity, toxicity, and mortality of patients with PMP treated by cytoreductive surgery (CRS) with intraperitoneal hyperthermic perfusion (IPHP).
METHODS: Thirty-three patients with PMP (21 males and 12 females) were enrolled in a phase II clinical trial. One patient underwent surgery twice because of disease recurrence. CRS was performed with peritonectomy procedures. The closed abdomen technique was employed for IPHP with use of cisplatin (25 mg/m2/L) plus mitomycin-C (3.3 mg/m2/L) for 60 minutes under hyperthermic conditions (42.5 degrees C).
RESULTS: Thirty-one patients (92%) were optimally cytoreduced. Five-year overall survival, progression-free survival, and locoregional progression-free survival rates were 97%, 43%, and 59%, respectively. Grade II and grade III morbidity was observed in 5 patient (15%) and 6 patients (18%), respectively. There was one treatment-related death (3%), 21 days after treatment.
CONCLUSIONS: CRS associated with IPHP permitted complete tumor removal with an acceptable morbidity and mortality for patients with PMP. This study confirms the efficacy of the combined treatment in terms of long-term survival and local disease control.
- Heat penetration in locally applied hyperthermia in the abdomen during intra-operative hyperthermic intraperitoneal chemotherapy.
van Ruth S, Verwaal VJ, Hart AA, van Slooten GW, Zoetmulder FA.
Department of Surgical Oncology, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Hospital, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands.
Anticancer Res. 2003 Mar-Apr;23(2B):1501-8. Abstract quote
BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) with mitomycin C has been applied following cytoreductive surgery for various peritoneal surface malignancies. The aim of this study was to evaluate heat penetration in the abdomen during 10 HIPEC procedures.
MATERIALS AND METHODS: Temperature measurements were taken at 5 levels through the abdominal wall. Core temperature and room temperature were also measured. The relationships between the temperature gradient and room or core temperature were studied.
RESULTS: At the start of perfusion, the temperature was estimated on average to be 40.6 degrees C at the first level, then it decreased by 1.7 degrees C (SD 1.0 degree C, p = 0.0001) in the first mm. In outward direction, it decreases by a further 1.5 degrees C per cm (SD 0.3 degree C/cm, p < 0.0001). The core temperature influenced the temperature gradient; the room temperature was not found to be a significant factor. At the end of perfusion, the temperature is estimated on average to be 40.1 degrees C at the first level, then it decreased by 0.8 degree C (SD 0.7 degree C, p = 0.011) in the first mm. In an outward direction, it decreased by a further 1.7 degrees C per cm (SD 0.4 degree C/cm, p = 0.0001). No evidence of an association between the temperature gradient and the room temperature or the core temperature was observed.
CONCLUSION: Hyperthermia used during HIPEC procedures has a limited penetration depth. The slope in temperature seems to be related to the core temperature.SURGERY Clinical effectiveness and costs of the Sugarbaker procedure for the treatment of pseudomyxoma peritonei.
Bryant J, Clegg AJ, Sidhu MK, Brodin H, Royle P, Davidson P.
Southampton Health Technology Assessments Centre, Wessex Institute for Health Research and Development, Southampton, UK.
Health Technol Assess. 2004 Feb;8(7):iii, 1-54. Abstract quote
OBJECTIVES: This systematic review examines the clinical and cost-effectiveness of the Sugarbaker procedure for treating pseudomyxoma peritonei (PMP) and the costs of the procedure in the UK.
DATA SOURCES: Electronic databases, bibliographies of related papers and experts in the field were used as sources for English language studies available up to September 2002.
REVIEW METHODS: Evidence of the clinical effectiveness of the Sugarbaker procedure for PMP was synthesised through a narrative review with full tabulation of results of all included studies. The economic modelling used a Monte-Carlo simulation model populated with UK price data to estimate likely UK costs.
RESULTS: Five retrospective case-series reports assessing the Sugarbaker procedure met the inclusion criteria for the review, although they were found to be of poor quality when judged against standard criteria for assessing methodological standard. There appears to be some benefit for people with PMP who undergo treatment with the Sugarbaker procedure. Commonly reported complications of the Sugarbaker procedure were anastomotic leaks, fistula formation, wound infection, small bowel perforations/obstructions and pancreatitis. One costing study of poor methodological quality and set in the USA was found. This study, together with UK unit price data and expert advice, was used to populate a Monte-Carlo simulation model to estimate the marginal cost of operating a service to provide treatment for PMP using the Sugarbaker technique rather than standard treatment. The results of the Monte-Carlo simulation model showed that the cost for one patient over a maximum of 5 years would be about 9700 British pounds, with a standard deviation of about 1300 British pounds (although costs incurred in setting up the specific service or training the staff were not included). The US study showed a ten-fold higher cost. The Monte-Carlo analysis showed that the variation around the mean was not very high. The most likely factor influencing the variation of the costs was the length of procedure. No sensitivity analysis could be done of the alternative treatment.
CONCLUSIONS: The economic results should be seen as merely an example of the likely marginal costs of the Sugarbaker procedure, as more information about the current alternative is required. Trained and experienced staff are required to implement the procedure and inevitably time and cost will be involved in developing the appropriate teams. Although the procedure requires some specialist equipment and maintenance, such as smoke evacuators, these should have limited effect on setting up the service. PMP is a relatively rare condition with approximately 50 new cases per year in the UK and the impact of an increase in the demand for services should be limited. Evidence is needed for the effectiveness of maximal cytoreductive surgery compared with surgical debulking, using different intraoperative intraperitoneal chemotherapy strategies, and for the effectiveness of treatments in patients who have residual disease following maximal efforts at cytoreduction. Further research involving high-quality prospective cohort studies with economic evaluations would be valuable.Am J Surg Pathol 1991;15:415-429
Hum Pathol 1995;26:509-524
Int J Gynecol Pathol 1997;16:1-9
Am J Pathol 1999;154:1849-1855
Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.
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