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Malignant Chest Wall Endometriosis: A Case Report and Literature Review
CASE REPORT CASE REPORT
Malignant Chest Wall Endometriosis: A Case Report and Literature Review Anita Agrawal, MBBS, FRCSC,1 Jill Nation, MD, FRCSC,2 Prafull Ghatage, MB, FRCSC,2 Pamela Chu, MD, FRCSC,2 Sue Ross, MSc, PhD,2,3,4 Anthony Magliocco, MD, FRCPC, FACP5,6 1
Department of Obstetrics and Gynaecology, Division of Gynaecologic Oncology, University of Calgary, Calgary AB
2
Department of Obstetrics and Gynaecology, University of Calgary, Calgary AB
3
Department of Family Medicine, University of Calgary, Calgary AB
4
Department of Community Health Sciences, University of Calgary, Calgary AB
5
Department of Pathology and Laboratory Medicine, University of Calgary, Calgary AB
6
Tom Baker Cancer Centre, Calgary AB
Abstract Background: Endometriosis usually affects women in their reproductive years. Most commonly, the pelvic organs are involved. Involvement of the chest wall after hysterectomy is rare. The incidence of malignant transformation is less than 1% for ovarian endometriosis, but is unknown for extraovarian endometriosis. Case: A 47-year-old woman who had undergone hysterectomy and bilateral salpingo-oophorectomy for endometriosis presented four years after surgery with a well-differentiated endometrioid adenocarcinoma arising in the background of endometriosis in the right chest wall. The tumour was resected, and the patient received six courses of adjuvant chemotherapy. Conclusion: Women with endometriosis-associated cancer require individualized management options, depending upon the histopathology and stage of the cancer.
Résumé Contexte : L’endométriose affecte habituellement les femmes au cours de leurs années de fertilité. D’ordre général, les organes pelviens sont mis en cause. La mise en cause de la paroi thoracique à la suite de l’hystérectomie est rare. Bien que l’incidence de la transformation maligne soit inférieure à 1 % pour ce qui est de l’endométriose ovarienne, elle demeure inconnue pour ce qui est de l’endométriose extra-ovarienne. Cas : Une femme de 47 ans ayant subi une hystérectomie et une salpingo-ovariectomie bilatérale en raison d’une endométriose présentait, quatre ans après cette chirurgie, un adénocarcinome endométrioïde bien différencié apparaissant en arrière-plan d’une endométriose logée dans la paroi thoracique droite. La tumeur a été réséquée et la patiente a reçu six traitements de chimiothérapie adjuvante.
Key Words: Chest wall endometriosis, soft tissue endometriosis, extra-ovarian endometriosis, carcinoma in endometriosis, adenocarcinoma Competing Interests: None declared. Received on October 21, 2008 Accepted on December 12, 2008
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l JUNE JOGC JUIN 2009
Conclusion : Les femmes qui présentent un cancer associé à l’endométriose nécessitent des options de prise en charge personnalisées, en fonction de l’histopathologie et du stade du cancer en question. J Obstet Gynaecol Can 2009;31(6):538–541
INTRODUCTION
ndometriosis is a condition in which functioning endometrial tissue (stroma and glands) is present outside the uterine cavity or myometrium.1 It is found in 8% to 15% of all menstruating women, mostly in the group aged 25 to 35 years,2,3 and in 2% to 5% of postmenopausal women. The most common location is within the pelvis.4 Extrapelvic endometriosis refers to endometriosis found at other body sites. The incidence of extrapelvic endometriosis is considerably lower than pelvic endometriosis; virtually any organ can be affected, but the true prevalence is unknown.1,5 Endometriosis involving the bladder, intestine, appendix, surgical scars, umbilicus, hernia sacs, thorax, kidney, and extremities has been described in case reports.6
E
The gastrointestinal tract is the most common site for extrapelvic endometriosis. Thoracic endometriosis is the most common site of endometriosis outside the abdominal cavity. It affects an older population and occurs at an average of five years later than the age at diagnosis of pelvic endometriosis. Thoracic endometriosis usually involves diaphragmatic pleura and lung parenchyma, and lesions are usually solitary.1 It usually presents with symptoms and signs of pneumothorax, hemothorax, hemoptysis, or chest pain.4,6 Lesions of the right chest are more common than the left, and the ratio of right-sided to left-sided
Malignant Chest Wall Endometriosis: A Case Report and Literature Review
involvement is at least 9:1. The incidence of concurrent pelvic endometriosis is between 50% and 80%.1,4 The soft tissue of the chest wall is a very rare site for endometriosis. Only one case report of chest wall endometriosis7 was identified in a literature search. Cancers arise in approximately 1% (0.8%–1.3%) of cases of ovarian endometriosis.8,9 The incidence of malignant transformation of extraovarian endometriosis is extremely low; less than 70 cases have been reported, the first case being identified in 1925.1,8,10–12 Of reported cases, the ovary accounted for 78% of cases of malignant transformation, and 22% occurred in extraovarian endometriosis.13–15 No cases of malignant transformation in thoracic endometriosis or endometriosis in chest wall soft tissue have been reported. One case of sarcoma arising from pleural endometriosis has been reported.16 Extrapelvic disease may represent metastatic spread.17 The suggested criteria for malignant transformation of endometriosis include (1) coexisting benign endometriosis and malignant transformation in continuity; (2) demonstration of cancer arising in the tissue and not invading it from another source; and (3) presence of tissue resembling endometrial stroma and surrounding characteristic glands.10,18 Endometrioid carcinoma and clear cell carcinoma are the most common histopathologic types of cancer reported in women with ovarian and extraovarian endometriosis.8,9 Non-epithelial tumours are seen more often in association with extraovarian endometriosis, and clear cell adenocarcinoma and adenosarcomas are the two most common malignancies arising in extraovarian endometriosis.8,13,15,19 The development of ascites is attributed to the rupture of endometrial cysts; the cyst contents act as an irritant to the serosal surfaces and result in ascites formation.20 Ruptured cysts may remain exposed, resulting in massive ascites.20 Ascitic fluid associated with endometriosis is usually exudate with reactive mesothelial cells, consistent with the proposed pathophysiology.20 THE CASE
A 47-year-old woman presented in 2003 with right-sided chest pain located between the seventh and eighth ribs. In 1998, she had undergone an exploratory laparotomy,
ABBREVIATIONS CT
computerized axial tomography
GnRH
gonadotrophin releasing hormone
NSAIDs non steroidal anti inflammatory drugs PET
positron emission tomography
omentectomy, drainage of 3.5 L of bloody ascitic fluid, bilateral wedge resection of both ovaries, and appendectomy after presenting with subacute abdominal pain. Histological assessment showed endometriosis in the omentum and serosal surface of the appendix with no evidence of malignancy. Treatment with a GnRH agonist was begun, but abdominal discomfort and menorrhagia persisted despite treatment for one year. In 2001, the patient agreed to undergo more definitive surgery and had a total abdominal hysterectomy and bilateral salpingooophorectomy. Benign endometriosis was identified on both fallopian tubes, on the uterine serosa, and on the right ovary. The left ovary showed extensive fibrosis. Eighteen months later, in 2003, the patient presented with intermittent right-sided chest pain. A soft tissue mass identified at the right costochondral junction was biopsied, with histopathologic findings of benign endometriosis with no atypia. A CT scan of the thorax showed a 3.6 ´ 1.8 cm mass close to right anterior eighth rib. A bone scan showed a focal bone abnormality involving the anterior eighth rib and mild changes in the seventh rib. The patient was treated with NSAIDs and a GnRH agonist with no improvement. On follow-up CT scan eight months later, an increase in the size of the right chest wall mass (to 6.1 ´ 3.1 cm) was noted. In early 2004, the patient was offered the options of surgical resection or radiation with GnRH agonist therapy. She declined these options and chose instead to take NSAIDs for pain and low-dose oral contraceptives for postmenopausal symptoms. In June 2005, she complained of increased pain in the right chest, and a repeat biopsy of the lesion showed histology consistent with endometriosis with complex hyperplasia and no atypia. A follow-up CT scan in October 2005 showed a further increase in the size of the mass (7.9 ´ 5.0 cm) with evidence of erosion at the anterior aspect of the eighth rib (Figure 1). In March 2006, the patient underwent resection of the right anterior chest wall (seventh and eighth ribs) with resection of 3–4 cm of diaphragmatic and costal margin and reconstruction using a mesh. The liver was noted not to be involved. Histological examination of the rib and surrounding fibromuscular tissue showed endometrioid adenocarcinoma (FIGO grade 1) with areas of chronic inflammation in a background of endometriosis (Figures 2 and 3). The margins of resection were clear. The carcinoma cells stained positive with CTK7, CTK 19, and vimentin, and an increased Ki67 index immunohistochemically suggested adenocarcinoma of endometrial origin. The carcinoma was ER positive (score 6/8); PR positive (score 6/8), and HER2/neu negative (Figure 4). JUNE JOGC JUIN 2009 l
539
CASE REPORT
After this surgery, the patient was offered six courses of carboplatin and paclitaxel chemotherapy. She suffered severe anaphylactic reactions to both paclitaxel and taxotere, and subsequently received single agent carboplatin for a total of six courses. Her serum CA 125 level ranged between 70 kU/L and 100 kU/L.
Figure 1. Computerized tomography scan of the thorax showing a 30 mm mass abutting the anterior chest wall
The patient was advised to take megestrol acetate 160 mg daily as prophylaxis against tumour recurrence. Although there was no evidence of disease elsewhere, there was a theoretical possibility that other foci of endometriosis might have undergone malignant transformation. A follow up PET scan to exclude metastases was inconclusive. While taking megestrol acetate, the patient gained significant weight and developed shortness of breath. In August 2008, CT scan of the chest showed no abnormality, and a whole body PET scan showed no metabolically active lesions. Subsequently, the patient chose to stop taking megestrol acetate. DISCUSSION
Endometriosis may undergo pathological changes similar to those seen in the endometrium.8 There is no specific tumour marker for malignant transformation. However, serum CA 125 levels can be elevated in any condition causing peritoneal irritation, including endometriosis.21 Serum CA 125 is used as a tumour marker in serum to monitor response to treatment in cases of epithelial ovarian cancer. Patients with endometriosis rarely have serum CA 125 levels > 100 U/mL, although levels of up to 106 IU/mL have been reported.9,21,22 In the case described, serum CA 125 levels ranged between 70 U/mL and 100 U/mL from the time of initial presentation in 1998. Several authors have suggested the possible role of endogenous or exogenous estrogen stimulation15,23 There have been several case reports of malignant transformation of extraovarian endometriosis in patients treated with unopposed estrogen after abdominal hysterectomy and bilateral salpingo-oophorectomy. Because of this, combined estrogen and progesterone treatment has been advised in such circumstances, instead of unopposed estrogen, in case of suspected residual endometriosis.8,9,16 The vagina was noted to be the commonest site for malignancy arising in extraovarian endometriosis during estrogen stimulation.23 Malignant transformation of endometriosis usually presents as a low grade tumour at an early stage.24 Malignant transformation of extragonadal endometriosis is rare. There is no established treatment protocol in this situation. Primary surgical treatment with resection of all disease is usually recommended.16 540
l JUNE JOGC JUIN 2009
Figure 2. Endometriotic glands and stroma within the fibrous tissue of the chest wall
In a series of 1000 patients, all patients with both ovarian and extraovarian endometriosis-associated cancer were treated with initial surgery followed by adjuvant chemotherapy in 71% of cases and radiotherapy in 50% of cases.8 Paclitaxel and platinum agents were the chemotherapeutic agents of choice, and there was a 75% clinical complete response. The authors did not find any difference in survival based on histology.19 Five-year survival in patients with extraovarian pelvic endometriosis of endometrioid cell type has been reported to be 82% to 100% for early stage disease, with a very poor prognosis (0–12% 5-year survival) for disseminated
Malignant Chest Wall Endometriosis: A Case Report and Literature Review
Figure 3. FIGO 1 endometrioid carcinoma within the fibrous tissue of the chest wall and ribs
Figure 4. Dark brown showing ER stain positive on immunohistochemistry
disease.9,13,16 Most patients with disseminated disease die within two years of diagnosis.24
8. Stern RC, Dash R, Bentley RC, Snyder MJ, Haney AF, Robboy SJ, et al. Malignancy in endometriosis: frequency and comparison of ovarian and extraovarian types. Int J Gynecol Pathol 2001;20:133–9.
The patient described in this report fulfills Sampson’s three histological criteria for diagnosis of malignant transformation of endometriosis.10 Her clinical presentation was atypical because her initial complaint was only chest pain; only one other case with a similar presentation has been reported.7 This patient’s case may provide a diagnostic dilemma, and a delay in diagnosis may occur in the absence of classical symptoms of thoracic endometriosis.
9. Benoit L, Arnould L, Cheynel N, Diane B, Causeret S, Machado A, et al. Malignant extraovarian endometriosis: a review. Eur J Surg Oncol 2006;32:6–11.
CONCLUSION
Extrapelvic endometriosis may persist and undergo malignant transformation even after bilateral oophorectomy. Women with endometriosis-associated cancer may require individualized management options. They should be treated based on the histopathology and stage of the cancer at the time of diagnosis. ACKNOWLEDGEMENTS
The woman whose story is told in this case report has provided written consent for its publication. REFERENCES 1. Jubanyik KJ, Comite F. Extrapelvic endometriosis. Obstet Gynecol Clin North Am 1997;24(2):411–40. 2. Vigano P, Parazzini F, Somigliana E, Vercelli E. Endometriosis: epidemiology and aetiological factors. Best Pract Res Clin Obstet Gynaecol 2004;18(2):177–200. 3. Stenchever MA, Droegemueller W, Herbst AL, Mishell DR. Comprehensive gynecology. 4th ed. St. Louis: Mosby;2001. 4. Honore GM. Extrapelvic endometriosis. Clin Obstet Gynecol 1999;42:699–711. 5. Markham SM, Carpenter SE, Rock A. Extrapelvic endometriosis. Obstet Gynecol Clin North Am 1989;16(1):193–219. 6. Alifano M, Trisolini R, Cancellieri A, Regnard JF. Thoracic endometriosis: current knowledge. Ann Thorac Surg 2006;81(2):761–9. 7. Yuen JSP, Chow PKH, Koong HN, Ho JMS, Girija R. Unusual sites (thorax and umbilical hernial sac) of endometriosis. J R Coll Surg Edinb 2001;46:313–5.
10. Sampson JA. Endometrial carcinoma of the ovary arising in endometrial tissue of that organ. Arch Surg 1925;10:1–72. 11. Brunson GL, Barclay DL, Sanders M, Araoz CA. Malignant extraovarian endometriosis: two case reports and review of the literature. Gynecol Oncol 1988;30:123–30. 12. Hitti IF, Glasberg SS, Lubicz S. Clear cell carcinoma arising in extraovarian endometriosis: Report of three cases and review of the literature. Gynecol Oncol 1990;39:314–20. 13. Heaps JM, Nieberg RK, Berek JS. Malignant neoplasms arising in endometriosis. Obstet Gynecol 1990;75:1023–8. 14. Ridley JH. Primary adenocarcinoma in implant of endometriosis. Obstet Gynecol 1966;27(2):261. 15. Gorp TV, Amant F, Neven P, Vergote I. Endometriosis and the development of malignant tumours of the pelvis. A review of literature. Best Pract Res Clin Obstet Gynaecol 2004;18(2)349–71. 16. Brooks JJ, Wheeler JE. Malignancy arising in extragonadal endometriosis: a case report and summary of the world literature. Cancer 1977;40:3065–73. 17. Seydel, AS, Sickel JS, Warner ED, Sax, HC. Extrapelvic endometriosis: diagnosis and treatment. Am J Surg 1996;171:239–41. 18. Scott RB. Malignant changes in endometriosis. Obstet Gynecol 1953;2:283–9. 19. Modesitt SC, Tortolero-Luna G, Robinson JB, Gershenson DM, Wolf JK. Ovarian and extraovarian endometriosis-associated cancer. Obstet Gynecol 2002;100:788–95. 20. Bernstein JS, Perlow V, Brenner JJ. Massive ascites due to endometriosis. Am J Dig Dis 1961;6:1–7. 21. Kowalczyk C, Doty A, Ginsburg KA. Serum CA-125 elevation associated with ovarian endometriosis. Gynecol endosco 1995;5:51–2. 22. Myers TJ, Arena B, Granai CO. Pelvic endometriosis mimicking advanced ovarian cancer: Presentation with pleural effusion, ascites, and elevated serum CA 125 level. Am J Obstet Gynecol 1995;173(3)966–7. 23. Gucer F, Pieber D, Arikan MG. Malignancy arising in extraovarian endometriosis during estrogen stimulation. Eur J Gynaecol Oncol 1998;19:39–41. 24. Abu MAE, Sinha P, Totoe L, McKune G. Endometrial cancer thirteen years after total abdominal hysterectomy and bilateral salpingo-oophorectomy and hormonal replacement therapy: a case report. Eur J Gynaecol Oncol 1997;482–3.
JUNE JOGC JUIN 2009 l
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Malignant Chest Wall Endometriosis: A Case Report and Literature Review Anita Agrawal, MBBS, FRCSC,1 Jill Nation, MD, FRCSC,2 Prafull Ghatage, MB, FRCSC,2 Pamela Chu, MD, FRCSC,2 Sue Ross, MSc, PhD,2,3,4 Anthony Magliocco, MD, FRCPC, FACP5,6 1
Department of Obstetrics and Gynaecology, Division of Gynaecologic Oncology, University of Calgary, Calgary AB
2
Department of Obstetrics and Gynaecology, University of Calgary, Calgary AB
3
Department of Family Medicine, University of Calgary, Calgary AB
4
Department of Community Health Sciences, University of Calgary, Calgary AB
5
Department of Pathology and Laboratory Medicine, University of Calgary, Calgary AB
6
Tom Baker Cancer Centre, Calgary AB
Abstract Background: Endometriosis usually affects women in their reproductive years. Most commonly, the pelvic organs are involved. Involvement of the chest wall after hysterectomy is rare. The incidence of malignant transformation is less than 1% for ovarian endometriosis, but is unknown for extraovarian endometriosis. Case: A 47-year-old woman who had undergone hysterectomy and bilateral salpingo-oophorectomy for endometriosis presented four years after surgery with a well-differentiated endometrioid adenocarcinoma arising in the background of endometriosis in the right chest wall. The tumour was resected, and the patient received six courses of adjuvant chemotherapy. Conclusion: Women with endometriosis-associated cancer require individualized management options, depending upon the histopathology and stage of the cancer.
Résumé Contexte : L’endométriose affecte habituellement les femmes au cours de leurs années de fertilité. D’ordre général, les organes pelviens sont mis en cause. La mise en cause de la paroi thoracique à la suite de l’hystérectomie est rare. Bien que l’incidence de la transformation maligne soit inférieure à 1 % pour ce qui est de l’endométriose ovarienne, elle demeure inconnue pour ce qui est de l’endométriose extra-ovarienne. Cas : Une femme de 47 ans ayant subi une hystérectomie et une salpingo-ovariectomie bilatérale en raison d’une endométriose présentait, quatre ans après cette chirurgie, un adénocarcinome endométrioïde bien différencié apparaissant en arrière-plan d’une endométriose logée dans la paroi thoracique droite. La tumeur a été réséquée et la patiente a reçu six traitements de chimiothérapie adjuvante.
Key Words: Chest wall endometriosis, soft tissue endometriosis, extra-ovarian endometriosis, carcinoma in endometriosis, adenocarcinoma Competing Interests: None declared. Received on October 21, 2008 Accepted on December 12, 2008
538
l JUNE JOGC JUIN 2009
Conclusion : Les femmes qui présentent un cancer associé à l’endométriose nécessitent des options de prise en charge personnalisées, en fonction de l’histopathologie et du stade du cancer en question. J Obstet Gynaecol Can 2009;31(6):538–541
INTRODUCTION
ndometriosis is a condition in which functioning endometrial tissue (stroma and glands) is present outside the uterine cavity or myometrium.1 It is found in 8% to 15% of all menstruating women, mostly in the group aged 25 to 35 years,2,3 and in 2% to 5% of postmenopausal women. The most common location is within the pelvis.4 Extrapelvic endometriosis refers to endometriosis found at other body sites. The incidence of extrapelvic endometriosis is considerably lower than pelvic endometriosis; virtually any organ can be affected, but the true prevalence is unknown.1,5 Endometriosis involving the bladder, intestine, appendix, surgical scars, umbilicus, hernia sacs, thorax, kidney, and extremities has been described in case reports.6
E
The gastrointestinal tract is the most common site for extrapelvic endometriosis. Thoracic endometriosis is the most common site of endometriosis outside the abdominal cavity. It affects an older population and occurs at an average of five years later than the age at diagnosis of pelvic endometriosis. Thoracic endometriosis usually involves diaphragmatic pleura and lung parenchyma, and lesions are usually solitary.1 It usually presents with symptoms and signs of pneumothorax, hemothorax, hemoptysis, or chest pain.4,6 Lesions of the right chest are more common than the left, and the ratio of right-sided to left-sided
Malignant Chest Wall Endometriosis: A Case Report and Literature Review
involvement is at least 9:1. The incidence of concurrent pelvic endometriosis is between 50% and 80%.1,4 The soft tissue of the chest wall is a very rare site for endometriosis. Only one case report of chest wall endometriosis7 was identified in a literature search. Cancers arise in approximately 1% (0.8%–1.3%) of cases of ovarian endometriosis.8,9 The incidence of malignant transformation of extraovarian endometriosis is extremely low; less than 70 cases have been reported, the first case being identified in 1925.1,8,10–12 Of reported cases, the ovary accounted for 78% of cases of malignant transformation, and 22% occurred in extraovarian endometriosis.13–15 No cases of malignant transformation in thoracic endometriosis or endometriosis in chest wall soft tissue have been reported. One case of sarcoma arising from pleural endometriosis has been reported.16 Extrapelvic disease may represent metastatic spread.17 The suggested criteria for malignant transformation of endometriosis include (1) coexisting benign endometriosis and malignant transformation in continuity; (2) demonstration of cancer arising in the tissue and not invading it from another source; and (3) presence of tissue resembling endometrial stroma and surrounding characteristic glands.10,18 Endometrioid carcinoma and clear cell carcinoma are the most common histopathologic types of cancer reported in women with ovarian and extraovarian endometriosis.8,9 Non-epithelial tumours are seen more often in association with extraovarian endometriosis, and clear cell adenocarcinoma and adenosarcomas are the two most common malignancies arising in extraovarian endometriosis.8,13,15,19 The development of ascites is attributed to the rupture of endometrial cysts; the cyst contents act as an irritant to the serosal surfaces and result in ascites formation.20 Ruptured cysts may remain exposed, resulting in massive ascites.20 Ascitic fluid associated with endometriosis is usually exudate with reactive mesothelial cells, consistent with the proposed pathophysiology.20 THE CASE
A 47-year-old woman presented in 2003 with right-sided chest pain located between the seventh and eighth ribs. In 1998, she had undergone an exploratory laparotomy,
ABBREVIATIONS CT
computerized axial tomography
GnRH
gonadotrophin releasing hormone
NSAIDs non steroidal anti inflammatory drugs PET
positron emission tomography
omentectomy, drainage of 3.5 L of bloody ascitic fluid, bilateral wedge resection of both ovaries, and appendectomy after presenting with subacute abdominal pain. Histological assessment showed endometriosis in the omentum and serosal surface of the appendix with no evidence of malignancy. Treatment with a GnRH agonist was begun, but abdominal discomfort and menorrhagia persisted despite treatment for one year. In 2001, the patient agreed to undergo more definitive surgery and had a total abdominal hysterectomy and bilateral salpingooophorectomy. Benign endometriosis was identified on both fallopian tubes, on the uterine serosa, and on the right ovary. The left ovary showed extensive fibrosis. Eighteen months later, in 2003, the patient presented with intermittent right-sided chest pain. A soft tissue mass identified at the right costochondral junction was biopsied, with histopathologic findings of benign endometriosis with no atypia. A CT scan of the thorax showed a 3.6 ´ 1.8 cm mass close to right anterior eighth rib. A bone scan showed a focal bone abnormality involving the anterior eighth rib and mild changes in the seventh rib. The patient was treated with NSAIDs and a GnRH agonist with no improvement. On follow-up CT scan eight months later, an increase in the size of the right chest wall mass (to 6.1 ´ 3.1 cm) was noted. In early 2004, the patient was offered the options of surgical resection or radiation with GnRH agonist therapy. She declined these options and chose instead to take NSAIDs for pain and low-dose oral contraceptives for postmenopausal symptoms. In June 2005, she complained of increased pain in the right chest, and a repeat biopsy of the lesion showed histology consistent with endometriosis with complex hyperplasia and no atypia. A follow-up CT scan in October 2005 showed a further increase in the size of the mass (7.9 ´ 5.0 cm) with evidence of erosion at the anterior aspect of the eighth rib (Figure 1). In March 2006, the patient underwent resection of the right anterior chest wall (seventh and eighth ribs) with resection of 3–4 cm of diaphragmatic and costal margin and reconstruction using a mesh. The liver was noted not to be involved. Histological examination of the rib and surrounding fibromuscular tissue showed endometrioid adenocarcinoma (FIGO grade 1) with areas of chronic inflammation in a background of endometriosis (Figures 2 and 3). The margins of resection were clear. The carcinoma cells stained positive with CTK7, CTK 19, and vimentin, and an increased Ki67 index immunohistochemically suggested adenocarcinoma of endometrial origin. The carcinoma was ER positive (score 6/8); PR positive (score 6/8), and HER2/neu negative (Figure 4). JUNE JOGC JUIN 2009 l
539
CASE REPORT
After this surgery, the patient was offered six courses of carboplatin and paclitaxel chemotherapy. She suffered severe anaphylactic reactions to both paclitaxel and taxotere, and subsequently received single agent carboplatin for a total of six courses. Her serum CA 125 level ranged between 70 kU/L and 100 kU/L.
Figure 1. Computerized tomography scan of the thorax showing a 30 mm mass abutting the anterior chest wall
The patient was advised to take megestrol acetate 160 mg daily as prophylaxis against tumour recurrence. Although there was no evidence of disease elsewhere, there was a theoretical possibility that other foci of endometriosis might have undergone malignant transformation. A follow up PET scan to exclude metastases was inconclusive. While taking megestrol acetate, the patient gained significant weight and developed shortness of breath. In August 2008, CT scan of the chest showed no abnormality, and a whole body PET scan showed no metabolically active lesions. Subsequently, the patient chose to stop taking megestrol acetate. DISCUSSION
Endometriosis may undergo pathological changes similar to those seen in the endometrium.8 There is no specific tumour marker for malignant transformation. However, serum CA 125 levels can be elevated in any condition causing peritoneal irritation, including endometriosis.21 Serum CA 125 is used as a tumour marker in serum to monitor response to treatment in cases of epithelial ovarian cancer. Patients with endometriosis rarely have serum CA 125 levels > 100 U/mL, although levels of up to 106 IU/mL have been reported.9,21,22 In the case described, serum CA 125 levels ranged between 70 U/mL and 100 U/mL from the time of initial presentation in 1998. Several authors have suggested the possible role of endogenous or exogenous estrogen stimulation15,23 There have been several case reports of malignant transformation of extraovarian endometriosis in patients treated with unopposed estrogen after abdominal hysterectomy and bilateral salpingo-oophorectomy. Because of this, combined estrogen and progesterone treatment has been advised in such circumstances, instead of unopposed estrogen, in case of suspected residual endometriosis.8,9,16 The vagina was noted to be the commonest site for malignancy arising in extraovarian endometriosis during estrogen stimulation.23 Malignant transformation of endometriosis usually presents as a low grade tumour at an early stage.24 Malignant transformation of extragonadal endometriosis is rare. There is no established treatment protocol in this situation. Primary surgical treatment with resection of all disease is usually recommended.16 540
l JUNE JOGC JUIN 2009
Figure 2. Endometriotic glands and stroma within the fibrous tissue of the chest wall
In a series of 1000 patients, all patients with both ovarian and extraovarian endometriosis-associated cancer were treated with initial surgery followed by adjuvant chemotherapy in 71% of cases and radiotherapy in 50% of cases.8 Paclitaxel and platinum agents were the chemotherapeutic agents of choice, and there was a 75% clinical complete response. The authors did not find any difference in survival based on histology.19 Five-year survival in patients with extraovarian pelvic endometriosis of endometrioid cell type has been reported to be 82% to 100% for early stage disease, with a very poor prognosis (0–12% 5-year survival) for disseminated
Malignant Chest Wall Endometriosis: A Case Report and Literature Review
Figure 3. FIGO 1 endometrioid carcinoma within the fibrous tissue of the chest wall and ribs
Figure 4. Dark brown showing ER stain positive on immunohistochemistry
disease.9,13,16 Most patients with disseminated disease die within two years of diagnosis.24
8. Stern RC, Dash R, Bentley RC, Snyder MJ, Haney AF, Robboy SJ, et al. Malignancy in endometriosis: frequency and comparison of ovarian and extraovarian types. Int J Gynecol Pathol 2001;20:133–9.
The patient described in this report fulfills Sampson’s three histological criteria for diagnosis of malignant transformation of endometriosis.10 Her clinical presentation was atypical because her initial complaint was only chest pain; only one other case with a similar presentation has been reported.7 This patient’s case may provide a diagnostic dilemma, and a delay in diagnosis may occur in the absence of classical symptoms of thoracic endometriosis.
9. Benoit L, Arnould L, Cheynel N, Diane B, Causeret S, Machado A, et al. Malignant extraovarian endometriosis: a review. Eur J Surg Oncol 2006;32:6–11.
CONCLUSION
Extrapelvic endometriosis may persist and undergo malignant transformation even after bilateral oophorectomy. Women with endometriosis-associated cancer may require individualized management options. They should be treated based on the histopathology and stage of the cancer at the time of diagnosis. ACKNOWLEDGEMENTS
The woman whose story is told in this case report has provided written consent for its publication. REFERENCES 1. Jubanyik KJ, Comite F. Extrapelvic endometriosis. Obstet Gynecol Clin North Am 1997;24(2):411–40. 2. Vigano P, Parazzini F, Somigliana E, Vercelli E. Endometriosis: epidemiology and aetiological factors. Best Pract Res Clin Obstet Gynaecol 2004;18(2):177–200. 3. Stenchever MA, Droegemueller W, Herbst AL, Mishell DR. Comprehensive gynecology. 4th ed. St. Louis: Mosby;2001. 4. Honore GM. Extrapelvic endometriosis. Clin Obstet Gynecol 1999;42:699–711. 5. Markham SM, Carpenter SE, Rock A. Extrapelvic endometriosis. Obstet Gynecol Clin North Am 1989;16(1):193–219. 6. Alifano M, Trisolini R, Cancellieri A, Regnard JF. Thoracic endometriosis: current knowledge. Ann Thorac Surg 2006;81(2):761–9. 7. Yuen JSP, Chow PKH, Koong HN, Ho JMS, Girija R. Unusual sites (thorax and umbilical hernial sac) of endometriosis. J R Coll Surg Edinb 2001;46:313–5.
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