Simultaneous occurrence of hepatic focal nodular hyperplasia and uterine endometrial stromal nodule in a patient having treated breast infiltrating ductal carcinoma
Journal
Acta Obstetricia et Gynecologica Scandinavica
Journal Volume
585
Journal Issue
586
Pages
585-586
Date Issued
2003
Author(s)
MING CHEN
Abstract
Uterine endometrial stromal nodule is a rare subtype of endometrial stromal tumor and is distinguished from low-grade endometrial stromal sarcoma by its well-circumscribed, noninfiltrating margin (1). It is composed of neoplastic cells resembling those found in the proliferative endometrium, and thus could be hormonally responsive. Progestin therapy is effective in treating low-grade endometrial stromal tumors (2). Benign liver tumors such as focal nodular hyperplasia and hepatic adenoma were rarely reported before the introduction of oral contraceptives in the early 1960s. An association between oral contraceptive use and focal nodular hyperplasia has been suggested (3). Breast carcinomas are also hormonally related (4). Here we report a patient having these three hormone-related tumors. A 35-year-old woman, gravida 4, para 2, with T2N0M0 breast cancer, who had never used oral contraceptives, had received modified radical mastectomy and adjuvant chemotherapy with monthly CMF (cyclophosphamide, methotrexate and 5-fluorouracil, 5-FU) for six courses till March, 1996 at a hospital (3 years and 1 month before admission to our hospital). Pathology showed infiltrating ductal carcinoma of the left breast without axillary lymph nodes metastasis. The tumor was 3 × 2 × 1 cm in size and located over the left upper quadrant of the left breast. The status of both estrogen receptor (ER) and progesterone receptor (PR) was negative at that time. In addition, fluctuations in serum liver enzyme levels had been noted for 6 years before the surgery and fatty liver was thought to be the cause from the findings of ultrasound and computed tomography (CT) scan. Serum alpha-fetoprotein (AFP) was not elevated. After the surgery and the adjuvant chemotherapy, the patient received regular follow-up at that hospital but no tamoxifen was given. The patient came to our hospital this time because of an intermittent abdominal pain over one year. Abdominal and pelvic ultrasound examinations revealed multiple hepatic nodules in various sizes along with two myomatous masses over the uterus. She was then admitted to our hospital with suspicion of tumor recurrence. On admission, serum tumor markers cancer antigen-125 (CA-125), cancer antigen 15-3 (CA15-3) and carcinoembryonic antigen (CEA) were normal. Panendoscopy and double-contrast radiography of the lower gastrointestinal tract both revealed no evidence of tumor. However, abdominal magnetic resonance imaging (MRI) revealed multiple hepatic tumors with one of them suspected metastatic because of its irregular margin. Angiography of the celiac trunk and the superior mesenteric artery could not determine the nature of the hepatic tumors. Biopsy of the hepatic tumors was suggested. Menometrorrhagia had been noted since completion of the adjuvant CMF chemotherapy. The patient therefore asked for a concurrent biopsy of the hepatic nodules and a hysterectomy. A cavitron ultrasonic surgical aspirator was used for the liver biopsy and three hepatic nodules locating over segments II, IV and VI of the liver were removed. The operative findings of the gynecological field showed two fundal myoma-like masses (6 × 6 × 7 cm and 3 × 3 × 3 cm in size, respectively) and enlargement of the right ovary. Thus a right salpingo-oophorectomy was carried out in addition to a hysterectomy. Strikingly, pathology of the specimens showed that there were two hepatic focal nodular hyperplasias (Fig. 1), one hepatic fatty metamorphosis, one uterine leiomyoma and one uterine endometrial stromal nodule. The smaller uterine tumor revealed an endometrial stromal tumor consisting of monotonous round to ovoid cells resembling normal proliferative endometrial stromal cells along with abundant spiral arterioles. A typical leiomyomatous mass was noted in the center of the nodule, which suggested either coexistence of leiomyoma and endometrial stromal nodule or an endometrial stromal nodule with good smooth muscle differentiation (Fig. 2). The results of special staining for ER and PR were both positive in the endometrial stromal nodule and both negative in the hepatic focal nodular hyperplasia. A histological examination showed a focal nodular hyperplasia of the liver with its characteristic central scar formation (S). (Hemotoxylin–eosin stain, original magnification × 100.) A well-demarcated tumor (T) is revealed, in which the cells resembled the normal proliferative endometrial stromal cells. The border (indicated by arrows) of the tumor separated the neoplasm from the surrounding myometrium (M). There were also many spiral arterioles (A) interspersed within the tumor. These findings suggested an endometrial stromal tumor. (Hemotoxylin–eosin stain, original magnification × 100.) The patient was discharged 10 days after surgery. No progestin or other adjuvant therapy was given. Regular outpatient clinic follow-up showed no evidence of disease for more than 3 years (42 months). Estrogens are thought to be the principal regulators of growth and differentiation in normal breast tissue and are considered to play an important role in the tumorigenesis and progression of breast cancer (4). Ovarian ablation and adjuvant tamoxifen therapy are therefore used in some women with breast cancer to reduce recurrence and improve survival. A retrospective study demonstrated that the estrogenic effect of tamoxifen on the uterus is related to the occurrence of some uterine cancers (5). Endometrial stromal tumor is estrogen related and can be treated with progestin (2). Our present case suggests that an endometrial stromal tumor can also arise without the effect of tamoxifen in patients with treated breast cancer who still had an ovary. In addition, in attempting to determine the role of estrogen in the tumorigenesis of hepatic focal nodular hyperplasia, many researchers aimed to determine the levels of ER protein in tumor tissues and obtained different results. Different methods used in these studies may explain why they failed to achieve a consensus (3). Moreover, the rarities of these tumors also limited the possibility of a large-scale study to determine their nature and their relationship with sex steroids. Endometrial stromal tumor, hepatic focal nodular hyperplasia and breast carcinoma are all thought to be hormone related. Our case appears to be the first reported in the literature in which all these three tumors existed in the same woman. Although the assays for ER and PR failed to attribute the occurrences of these tumors to sex steroids in our patient, further studies to develop more sensitive and reliable methods are needed before concluding that coincidence is the causative factor in our case. Address for correspondence: Ming Chen Department of Obstetrics and Gynecology Changhua Christian Hospital No. 135, Nanhsiao Street 500, Changhua Taiwan e-mail: [email protected]
SDGs
Other Subjects
antineoplastic agent; cyclophosphamide; fluorouracil; methotrexate; abdominal pain; adult; article; breast carcinoma; cancer adjuvant therapy; cancer combination chemotherapy; cancer surgery; case report; clinical feature; computer assisted tomography; diagnostic imaging; female; follow up; human; human tissue; hysterectomy; image analysis; liver biopsy; liver tumor; mastectomy; menorrhagia; metrorrhagia; nodular hyperplasia; nuclear magnetic resonance imaging; priority journal; symptom; uterus tumor; Adult; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Carcinoma, Ductal, Breast; Comorbidity; Cyclophosphamide; Endometrial Stromal Tumors; Female; Fluorouracil; Focal Nodular Hyperplasia; Humans; Leiomyoma; Magnetic Resonance Imaging; Methotrexate; Neoplasms, Multiple Primary; Uterine Neoplasms
Type
journal article