|Ahead of print publication
Isolated acrometastasis: A rare presenting feature of endometrial carcinoma
Irappa V Madabhavi1, Apurva Patel2, Malay S Sarkar3, Mitul G Modi4, Suhas Aagre5
1 Department of Medical and Pediatric Oncology, Gujarat Cancer Research Institute, Ahmedabad, Gujarat, India
2 Department of Medical Oncology, Gujarat Cancer Research Institute, Ahmedabad, Gujarat, India
3 Department of Pulmonary Medicine, Indira Gandhi Medical College, Shimla, Himachal Pradesh, India
4 Department of Pathology, Gujarat Cancer Research Institute, Ahmedabad, Gujarat, India
5 Department of Medical Oncology, Asian Institute of Oncology, Mumbai, Maharashtra, India
Irappa V Madabhavi,
Department of Medical and Pediatric Oncology, Gujarat Cancer Research Institute, Ahmedabad, Gujarat
Source of Support: None, Conflict of Interest: None
The most common presenting feature of endometrial carcinoma (EC) is abnormal uterine bleeding. Bone metastasis, as a presenting feature of EC, is very unusual which is usually restricted to pelvis and vertebrae. The occurrence of foot metastasis is exceedingly rare. We report a case of a postmenopausal female presented with pain and swelling involving right foot. Biopsy revealed metastatic adenocarcinoma. The patient denied any history of vaginal bleeding or other gynecological symptoms. Bone scan suggested increased uptake in multiple tarsal bones. Uterine curettage confirmed the diagnosis of endometrial adenocarcinoma. The patient was successfully treated with debulking surgery, palliative radiotherapy to the right foot, bisphosphonates, and systemic chemotherapy with marked improvement in local symptoms and is under follow-up for the last 6 months after completion of the treatment. An extensive review of the literature, to the best of our knowledge, did not reveal many cases of acrometastasis as a presenting feature of EC.
Keywords: Acrometastasis, endometrial carcinoma, foot metastasis
| > Introduction|| |
Endometrial carcinoma (EC), one of the most common gynecological malignancies, usually presents with early-stage disease apparently confined to the uterus. Bone metastasis of EC is very unusual, incidence ranging from 2% to 15% which is generally restricted to pelvis and vertebrae., The occurrence of foot metastasis as an initial presentation is exceedingly rare. We hereby present a case of advanced EC with initial metastasis to the right foot.
| > Case Report|| |
Apparently healthy 66-year-old postmenopausal female presented to local physician with 1-month history of pain and swelling in the right foot. Local X-ray showed a suspicious lesion involving tarsal bones. On biopsy, it turned out to be a metastatic adenocarcinoma. The patient was referred to our center for further management. Despite repeated inquiry, the patient denied any history of vaginal bleeding, related gynecological symptoms as well as other gastrointestinal or genitourinary symptoms.
On examination, her height, weight, body mass index, and vitals were within normal range. The patient had swelling and local tenderness of the right foot. Per speculum examination did not reveal any abnormality. Hemogram, renal, and liver function tests were within normal limits except for the raised alkaline phosphatase. On further workup, computed tomography of the abdomen and pelvis revealed mildly enlarged uterus with endometrial thickness of 6 mm. Uterine curettage and histopathological examination of the biopsy specimen showed numerous, small, crowded glands with varying degrees of nuclear atypia, mitotic activity, and stratification, thus confirmed the diagnosis of well-differentiated endometrial adenocarcinoma [Figure 1]. Bone scan showed abnormal increased diffuse tracer uptake in multiple tarsal bones of the right foot [Figure 2]. Thus, her disease was classified as the International Federation of Gynecology and Obstetrics (FIGO) Stage IVb EC. The patient was managed with debulking surgery in the form of total abdominal hysterectomy with bilateral salpingo-oophorectomy, pelvic lymph node dissection, and paraaortic lymph node sampling. Pathology revealed FIGO Grade 1 endometrioid endometrial adenocarcinoma from histopathology specimen. Immunohistochemical staining revealed tumor cells positive for estrogen receptor and progesterone receptor. Later, the patient received palliative radiotherapy of 30 Gy in 10 fractions to the right foot and bisphosphonates. Palliative systemic chemotherapy consisting of paclitaxel (175 mg/m2) and carboplatin (area under the curve [AUC]-5) was given at an interval of 21 days for a total of six cycles. The patient tolerated very well to chemotherapy with marked improvement in local symptoms and is under regular follow-up for the last 6 months after the completion of treatment.
|Figure 1: Well-differentiated endometrial adenocarcinoma showing numerous, small, crowded glands with varying degrees of nuclear atypia, mitotic activity, and stratification. This often appears on a background of endometrial hyperplasia|
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|Figure 2: (a and b) Bone scan showed abnormal increased diffuse tracer uptake in multiple tarsal bones of the right foot|
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| > Discussion|| |
Endometrial cancer is one of the most common invasive cancers of the female genital tract. The most common presenting symptom is abnormal uterine bleeding that is seen in 75%–90% of cases. Endometrial cancer occurs most commonly in the postmenopausal period. About 70%–80% of cases are diagnosed with Stage I disease, 20%–25% in Stage II and III, and only 3% of the patients have Stage IV disease at the time of presentation.
The risk factors for endometrial cancer are obesity, excessive estrogen exposure, hypertension, and diabetes. Estrogen replacement therapy without the use of progesterone appears to increase the risk of endometrial cancer, taking both estrogen and progesterone in combination, as in most birth control pills, decreases the endometrial cancer risk. Other less common risk factors are nulliparity, polycystic ovary syndrome, early menarche, late menopause, and the use of tamoxifen.
The diagnosis of endometrial cancer is usually made by endometrial biopsy or dilatation and curettage. The most endometrial cancers are endometrioid adenocarcinoma (75%–80%), while nonendometrioid histologies (20%–25%) include papillary serous, clear cell, mucinous, squamous cell, transitional cell, and mixed types.
EC usually extends to cervix by local invasion, and hematogenous dissemination is relatively infrequent. In more advanced disease, the sites commonly affected outside the uterus are pelvic and paraaortic lymph nodes and the ovaries. The usual sites of distant metastasis are lung, liver, and brain.
Metastatic endometrial cancer lesions are predominantly found in the lymph nodes, omentum, lungs, and liver. The spread is typically from direct invasion or through the lymphovascular pathway. Endometrial cancer with metastasis to bone has been reported to occur in 2%–6% of all metastatic endometrial cancers. Of the reported cases of bony metastases, the most common locations have involved the appendicular skeleton with a high surgical stage and grade. Hematogenous dissemination is the most common route of bony metastasis. Metastasis to the foot and hand (acrometastasis) is extremely rare (0.007%–0.3%); metastasis to the feet is even rarer and has been reported in half to one-third of the rate for hand metastasis., Foot metastases are most commonly caused by tumors of the gastrointestinal or genitourinary tracts while metastases to the hand are usually seen with bronchogenic carcinomas.
The most common site of osseous metastases in EC is vertebrae, pelvic bones, ribs, and sternum. Isolated metastases to the bone extremities are extremely rare and thought to result from the hematological spread of cancer cells.
The most common staging system used for EC is FIGO staging. It divides patients into four stages. Our patient fits into Stage IVb FIGO staging system.
The treatment of endometrial cancer is dependent on the stage of the disease and the patient's performance status. Main modalities of treatment include surgery, radiotherapy, and chemotherapy. Early-stage endometrial cancer can often be treated with surgery and radiotherapy whereas the treatment of advanced stage includes multiagent chemotherapy regimens if tolerated with or without surgery and radiotherapy. Due to the safety and efficacy of carboplatin and paclitaxel in the management of other gynecologic malignancies, there is an interest in using this regimen as the first-line treatment in patients with advanced endometrial cancer. Six phase II studies have been published of previously untreated patients with advanced disease with overall response rates ranging from 40% to 63%. Hence, carboplatin and paclitaxel is an increasingly used regimen for advanced or metastatic EC; the response rate is about 40%–62%; and the overall survival is 13–29 months.,,,,,
The gynecologic oncology group has two ongoing Phase III studies addressing the question of first-line carboplatin and paclitaxel treatment: (1) GOG 249: Phase III study of pelvic radiation therapy versus vaginal cuff brachytherapy, followed by paclitaxel and/or carboplatin chemotherapy in patients with high-risk early-stage endometrial cancer; (2) GOG 258: Randomized Phase III trial of cisplatin and tumor volume-directed irradiation, followed by carboplatin and paclitaxel versus carboplatin and paclitaxel for optimally debulked advanced endometrial cancer.
If multi-agent chemotherapy regimens are contraindicated, then single-agent chemotherapy options include paclitaxel, cisplatin, carboplatin, doxorubicin, topotecan, and docetaxel. New biologic and molecular therapies are being assessed in clinical trials such as bevacizumab and temsirolimus with a response rate of 13.5% and 4%, respectively.
There is no consensus on the standard treatment of Stage IVb endometrioid EC. Prognosis is poor, and the treatment is predominantly palliative. A review of the literature reveals that the most common treatment for metastases to the bone involves surgical removal of the lesion (if possible), site-directed radiation therapy, and intravenous chemotherapy. In view of the metastatic and advanced nature of the disease, our patient was initially treated with debulking surgery, palliative radiotherapy to bony metastasis of right foot, followed by systemic chemotherapy. Based on the available data, we planned to give six cycles of paclitaxel (175 mg/m2) and carboplatin (AUC-5) at an interval of 21 days along with bisphosphonates. The patient tolerated chemotherapy well, and she is under regular follow-up for 6 months after the treatment completion at our institute for the recurrence of the disease.
The surveillance of the endometrial cancer patient requires history and physical examination every 3–6 monthly for 2–3 years followed by 6 monthly or annually. Imaging of the abdomen and pelvis only if clinically indicated. The patient should be educated regarding the symptoms of potential recurrence, lifestyle, obesity, exercise, sexual health, smoking cessation, and nutrition counseling.
| > Conclusion|| |
Despite the rarity of acrometastasis, there is a need to have a high index of suspicion for metastasis in patients with a history of EC who present with new-onset swelling, bony pain, or tenderness.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
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Conflicts of interest
There are no conflicts of interest.
| > References|| |
Manolitsas TP, Fowler JM, Gahbauer RA, Gupta N. Pain in the foot: Calcaneal metastasis as the presenting feature of endometrial cancer. Obstet Gynecol 2002;100:1067-9.
Cooper JK, Wong FL, Swenerton KD. Endometrial adenocarcinoma presenting as an isolated calcaneal metastasis. A rare entity with good prognosis. Cancer 1994;73:2779-81.
Abdul-Karim FW, Kida M, Wentz WB, Carter JR, Sorensen K, Macfee M, et al.
Bone metastasis from gynecologic carcinomas: A clinicopathologic study. Gynecol Oncol 1990;39:108-14.
Albareda J, Herrera M, Salva AL, Donas JG, Gonzalez R. Sacral metastasis in a patient with endometrial cancer: Case report and review of the literature. Gynecol Oncol 2008;111:583-8.
Johnston AD. Pathology of metastatic tumors in bone. Clin Orthop Relat Res 1970;73:8-32.
Healey JH, Turnbull AD, Miedema B, Lane JM. Acrometastases. A study of twenty-nine patients with osseous involvement of the hands and feet. J Bone Joint Surg Am 1986;68:743-6.
Libson E, Bloom RA, Husband JE, Stoker DJ. Metastatic tumours of bones of the hand and foot. A comparative review and report of 43 additional cases. Skeletal Radiol 1987;16:387-92.
Loizzi V, Cormio G, Cuccovillo A, Fattizzi N, Selvaggi L. Two cases of endometrial cancer diagnosis associated with bone metastasis. Gynecol Obstet Invest 2006;61:49-52.
Price FV, Edwards RP, Kelley JL, Kunschner AJ, Hart LA. A trial of outpatient paclitaxel and carboplatin for advanced, recurrent, and histologic high-risk endometrial carcinoma: Preliminary report. Semin Oncol 1997;24:S15-78-S15-82.
Hoskins PJ, Swenerton KD, Pike JA, Wong F, Lim P, Acquino-Parsons C, et al.
Paclitaxel and carboplatin, alone or with irradiation, in advanced or recurrent endometrial cancer: A phase II study. J Clin Oncol 2001;19:4048-53.
Scudder SA, Liu PY, Wilczynski SP, Smith HO, Jiang C, Hallum AV 3rd
, et al.
Paclitaxel and carboplatin with amifostine in advanced, recurrent, or refractory endometrial adenocarcinoma: A phase II study of the southwest oncology group. Gynecol Oncol 2005;96:610-5.
Sovak MA, Dupont J, Hensley ML, Ishill N, Gerst S, Abu-Rustum N, et al.
Paclitaxel and carboplatin in the treatment of advanced or recurrent endometrial cancer: A large retrospective study. Int J Gynecol Cancer 2007;17:197-203.
Pectasides D, Xiros N, Papaxoinis G, Pectasides E, Sykiotis C, Koumarianou A, et al.
Carboplatin and paclitaxel in advanced or metastatic endometrial cancer. Gynecol Oncol 2008;109:250-4.
Nomura H, Aoki D, Takahashi F, Katsumata N, Watanabe Y, Konishi I, et al.
Randomized phase II study comparing docetaxel plus cisplatin, docetaxel plus carboplatin, and paclitaxel plus carboplatin in patients with advanced or recurrent endometrial carcinoma: A Japanese gynecologic oncology group study (JGOG2041). Ann Oncol 2011;22:636-42.
Shigemitsu A, Furukawa N, Koike N, Kobayashi H. Endometrial cancer diagnosed by the presence of bone metastasis and treated with zoledronic acid: A case report and review of the literature. Case Rep Oncol 2010;3:471-6.
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