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Byline: Alan A. Thomay, MD; Matthew T. Then, MD; and Jeffrey M. Farma, MD
Chief Complaint
H.G., a 72-year-old obese woman, presents with a 6-month history of infrequent upper abdominal pain and nausea, along with non-specific gastrointestinal symptoms.
Relevant Medical History
• Hypertension
• Four uncomplicated vaginal deliveries (G4P4)
• Appendectomy
Physical Exam
• A central, nodular mass that is fixed to the anterior abdominal wall is palpable, without tenderness or inguinal adenopathy
• Pelvic examination shows a normal size uterus with no adnexal masses or nodularity
Social/Family History
• 30 pack-year smoking history
Relevant Laboratory Tests and Imaging Results Summarized on Slide 2
Based on the imaging results, an exploratory laparotomy performed.
• Results showed a large solid and cystic mass arising from the mesentery of the mid-ileum with invasion of the anterior abdominal wall (Slide 1)
• No evidence of peritoneal carcinomatosis or distant metastatic spread was noted, and the ovaries and uterus appeared grossly normal
• Pathologic examination of the resected tumor demonstrated an 18cm tumor arising in the mesentery and invading into the muscularis of the small intestine, with overlying mucosal ulceration and protrusion into the lumen (Slide 3)
• Sectioning of the ovaries revealed evidence of past endometriotic foci without associated malignancy
Submit your diagnosis to see full explanation.
Answer: Endometrioid adenocarcinoma
Explanation/Discussion
Clear cell carcinomas have a high glycogen content, causing their cells to have a clear appearance,1 whereas cells in papillary serous carcinoma generally form slit-like glandular spaces.2 Both of these tumors are aggressive uterine cancers and generally metastasize outside of the pelvis, unlike endometrioid carcinomas.
Endometrial stromal sarcomas only involve cells that resemble the endometrial stroma. They are metaplastic carcinomas, not a subtype of uterine sarcomas as previously believed, and require a whole-abdominal hysterectomy and a bilateral oophorectomy.1
As shown Slide 4, the carcinoma most resembles an endometrioid carcinoma. Her tumor was resected en bloc with involved small intestine and a portion of the anterior abdominal wall. Sectioning of the ovaries revealed evidence of past endometriotic foci without associated malignancy. These findings are suggestive of malignant transformation of extra-uterine endometrial implants.
Symptomatic endometriosis can affect up to 10% of women of reproductive age, yet drops to 2% to 5% of women during the postmenopausal period. Some authors believe the true incidence is higher.3 One third of all women affected with endometriosis are asymptomatic, but overlooked symptoms may include dysmenorrhea, dyspareunia, dyschezia, bloating, nausea, urinary pain or frequency, and abdominal, inguinal, pelvic, or back pain.
In patients suffering from chronic abdominal and/or pelvic pain, such as our patient, the incidence can be as high as 80%.4 Currently, there is debate whether the diagnosis of endometriosis is associated with a definite increase in the risk for various other malignancies.5
The first case of malignant endometriotic transformation of an ovary was described by Sampson in 1925.6 It is now estimated that 1% of endometriosis patients will develop an associated neoplasm, with three of four tumors arising in the ovary.7,8
The most frequent sites of involvement for extra-ovarian lesions include the rectovaginal septum, the colon, and the vagina, with 62% of patients having previously received estrogen replacement therapy.9 The small intestine and mesentery are involved in less than 1% of cases.
It has recently been suggested in endometriosis-associated ovarian malignancies that ARID1A functions as a tumor suppression gene and can be seen in preneoplastic lesions.10 The authors speculate that this would be among the earliest events in the transformation of endometriosis into cancer.
Presenting symptoms after malignant transformation are variable, but include pain, vaginal bleeding, GI dysfunction, and a pelvic mass. Although no specific biologic marker is available, patients may have elevated CA-125 levels, while patients with endometriosis rarely have levels greater than 100 IU/mL.11
Up to 90% of extra-ovarian endometriosis-associated malignancies are pure endometrioid adenocarcinomas, with endometrial stromal sarcoma being the second most common.12
However, in a recent review of the available case reports and literature, the differential diagnosis was broad, and includes: spindle cell sarcoma, squamous cell carcinoma, adenoacanthoma, carcinosarcoma, adenosquamous carcinoma, mixed germ cell tumor, clear cell carcinoma, adenofibroma, adenosarcoma, mullerian adenosarcoma, and atypical hyperplasia.13
The mainstay of therapy is operative resection with negative margins. Data on adjuvant chemoradiotherapy is lacking, although one series demonstrated that 71% of patients receive chemotherapy, 50% receive radiotherapy, and only 13% are clinically observed following resection.9
With endometrioid disease confined to the site of origin, the prognosis is excellent, with reports suggesting an 82% to 100% 5-year survival.8,14 Unfortunately, patients presenting with peritoneal carcinomatosis have a very poor 5-year survival, ranging from 0% to 12%.
References
1. Acharya S, Hensley ML, Montag AC, Fleming GF. Rare uterine cancers. Lancet Oncol. 2005 Dec;6(12):961-71
2. Gehrig PA, Groben PA, Fowler WC, et al. Noninvasive papillary serous carcinoma of the endometrium. Obstet Gynecol. 2001 Jan;97(1):153-7
3. Punnonen R, Klemi PJ, Nikkanen V. Postmenopausal endometriosis. Eur J Obstet Gynecol Reprod Biol. 1980 Dec;11(3):195-200.
4. Carter JE. Combined hysteroscopic and laparoscopic findings in patients with chronic pelvic pain. J Am Assoc Gynecol Laparosc. 1994 Nov;2(1):43-7.
5. Somigliana E, Vigano P, Parazzini F, et al. Association between endometriosis and cancer: A comprehensive review and a critical analysis of clinical and epidemiological evidence. Gynecol Oncol. 2006; 101:331-41
6. Sampson JA. Endometrial carcinoma of ovary, arising endometrial tissue in that organ. Arch Surg. 1925; 10:1-72. 2.
7. Mostoufizadeh M, Scully RE. Malignant tumors arising in endometriosis. Clin Obstet Gynecol. 1980 Sep;23(3):951-63.
8. Heaps JM, Nieberg RK, Berek JS. Malignant neoplasms arising in endometriosis. Obstet Gynecol. 1990 Jun;75(6):1023-8.
9. Modesitt SC, Tortolero-Luna G, Robinson JB, et al. Ovarian and extraovarian endometriosis-associated cancer. Obstet Gynecol. 2002 Oct;100(4):788-95.
10. Wiegand KC, Shah SP, Al-Agha OM, et al. ARID1A mutations in endometriosis-associated ovarian carcinomas. N Engl J Med. 2010; 363:1532-43
11. Koninckx PR, Muyldermans M, Moerman P, et al. CA 125 concentrations in ovarian ‘chocolate’ cyst fluid can differentiate an endometriotic cyst from a cystic corpus luteum. Hum Reprod. 1992 Oct;7(9):1314-7.
12. Brunson GL, Barclay DL, Sanders M, et al. Malignant extraovarian endometriosis: two case reports and review of the literature. Gynecol Oncol. 1988 May;30(1):123-30.
13. Benoit L, Arnould L, Cheynel N, et al. Malignant extraovarian endometriosis: a review. Eur J Surg Oncol. 2006 Feb;32(1):6-11
14. Brooks JJ, Wheeler JE. Malignancy arising in extragonadal endometriosis: a case report and summary of the world literature. Cancer. 1977 Dec;40(6):3065-73.
QUESTION
