Abstract
Abstract
Background:
Embryonic mammary tissue may fail to regress, resulting in ectopic breast tissue in areas outside the breasts, including within the vulva. In exceedingly few instances, this tissue may undergo malignant transformation.
Cases:
Three cases of vulvar adenocarcinoma arising in ectopic breast tissue are presented. Tissue biopsy confirmed the diagnosis. Surgical resection was performed for these patients. Adjuvant therapy was individually tailored to the metastatic spread and receptor positivity of the tumors, including chemotherapy, radiation therapy, and hormonal therapy.
Results:
Radiation therapy was tolerated well by these patients, without undue side-effects. All three patients are alive and well 3 and 4 years post treatment.
Conclusions:
Treating patients with this vulvar malignancy with the established guidelines for breast carcinoma appears to be a rational approach with successful outcomes as occurred in the 3 patients presented in this report. (J GYNECOL SURG 33:22)
Introduction
I
This article presents three cases of primary adenocarcinoma of the vulva arising in ectopic breast tissue. These three cases all presented to and were treated by one of the authors (D.C.K.) between April 2011 and June 2012. From January 2011 to December 2012, an average of 32 cases per year of primary invasive vulvar cancer were seen at Women's Cancer Care Associates, Albany, NY, which serves as the gynecologic oncology referral center for eastern upstate New York State. These cases were treated in a prospective manner by a multidisciplinary team consisting of gynecologic, medical, and radiation oncologists at St. Peter's Hospital, Albany, NY. By combining the guidelines for vulvar cancer with those for breast cancer, the treatment of these patients was tailored in an effort to minimize their morbidity and induce durable responses.
Cases and Results
Case A
Patient A was a 75-year-old white female who presented with a 4-month history of intermittent bleeding from a persistent 1-cm, ulcerated, right labial mass. The mass was excised by her primary gynecologist, and pathology testing revealed an invasive adenocarcinoma with negative margins and focal perineural invasion present. Immunohistochemical (IHC) stains suggested a primary adenocarcinoma of the vulva (positive cytokeratins 7 and LMW and p63). Computed tomography (CT) scanning of the pelvis was negative for metastatic disease. A mammogram showed two nodular densities in the outer quadrant of the left breast corresponding to small cysts with no solid mass on ultrasound. The patient underwent an excision allowing for a 2-cm margin circumferentially around the previous excision site. Because of the patient's anatomy, this necessitated a right radical hemivulvectomy. The patient was injected for testing sentinel nodes, but none were positive. A right inguinal lymph-node dissection was performed removing the superficial and deep inguinal lymph nodes.
Final pathology testing showed that the vulva was negative for residual disease; however, 2/6 superficial inguinal nodes were positive for metastatic high-grade adenocarcinoma, as were 1/2 deep inguinal nodes. The tumor was found to be estrogen receptor (ER)–positive (80%), progesterone receptor (PR)–negative and 3+ Her2/neu by IHC. In addition, both mammaglobin and gross cystic-disease fluid protein (GCDFP)–15 immunostaining were positive, consistent with adenocarcinoma arising in ectopic mammary tissue. A postoperative positron emission tomography (PET) scan revealed a hypermetabolic obturator lymph node measuring 0.9 × 1.7 cm with a maximum SUV of 14 and a common femoral node measuring 1.4 × 1.6 cm with a maximum standard uptake value (SUV) of 20.2, consistent with metastatic disease.
Radiation therapy was given as an integrated boost with intensity modulated radiation therapy (IMRT) techniques without treatment at the primary site. The patient received radiation therapy to the involved and PET positive inguinal and pelvic lymph nodes. A total dose of 5320 cGy was delivered in 28 fractions of 190 cGy/day, utilizing 7 IMRT fields. The uninvolved right pelvic lymph nodes extending to the aortic bifurcation were treated concomitantly with 4900 cGy in 28 fractions of 175 cGy/day. She also received concomitant sensitizing cisplatin chemotherapy through her radiation therapy, dosed at 40 mg/m2 weekly, for 4 weeks. She experienced diarrhea and fatigue but managed to tolerate her treatment well.
Following completion of her radiation therapy, this patient was treated with trastuzumab in combination with chemotherapy. She received 13 doses of trastuzumab weekly with an initial dose of 4 mg/kg and subsequent maintenance doses of 2 mg/kg. Initially, the patient received docetaxel (dosed at 75 mg/m2) and carboplatin (6 area under the curve); however, she experienced severe toxicity and treatment was discontinued after 1 cycle. Chemotherapy was then initiated with 600 mg/m2 of cyclophosphamide, 40 mg/m2 of methotrexate, and 600 mg/m2 of 5-fluorouracil (all 3 drugs = CMF). She experienced severe weakness and debilitation after her fourth cycle of CMF and required hospitalization. She then decided not to pursue any further treatment. PET/CT scanning post treatment and in follow-up have been negative for residual disease. This patient continues to be followed, and four years after surgery, has no evidence of disease.
Case B
Patient B was a 59-year-old white female who presented with a 4-month history of a persistent right vulvar mass. Magnetic resonance imaging (MRI) of her pelvis showed a small enhancing nodule in the right vulva without any other masses or lymphadenopathy noted. A vulvar biopsy revealed an adenocarcinoma with mucinous/colloid features, consistent with adenocarcinoma arising in ectopic mammary tissue. The patient underwent radical excision of the primary site, allowing for a 2-cm margin. The patient's anatomy required a right hemivulvectomy. A right sentinel inguinal lymph-node biopsy was also performed.
On final pathology testing, the vulva showed a 9-mm invasive mucinous (“colloid”) adenocarcinoma with mammary-type features. One of two sentinel lymph nodes showed the presence of metastatic adenocarcinoma. IHC stains revealed the tumor to be ER-, CK7-, and mammaglobin-positive and weakly positive for PR and carcinoembryonic antigen. The tumor was S-100-, GCDFP-, and CK-20 negative. Fluorescence in situ hybridization analysis was negative for Her2/neu. Breast MRI was negative.
The patient was initially treated with four cycles of docetaxel and cyclophosphamide dosed at 75 mg/m2 and 600 mg/m2, respectively. She experienced severe bone pain following the first cycle, and the docetaxel was dose reduced to 60 mg/m2 for the remaining three cycles. Following completion of her chemotherapy, adjuvant radiation therapy was initiated. The right vulva, right inguinal region and right pelvic lymph nodes to the level of L5–S1 were treated with a 6-field IMRT technique to deliver 4500 cGy, with a daily fraction of 180 cGy. After the delivery of 4500 cGy, the right vulva and inguinal areas were boosted with an additional 1260 cGy using IMRT for a cumulative dose of 5760 cGy.
Upon completion of radiation therapy, this patient was started on 20 mg of tamoxifen p.o. daily for an anticipated five years. Four years after her surgery, this patient has no clinical evidence of disease.
Case C
Patient C was a 67 year-old white female who presented with a 6-month history of an enlarging right vulvar mass. A 3-cm mass from the anterior portion of the right labium majora was excised by her primary gynecologist. On final pathology, the vulva showed a mucinous adenocarcinoma involving the subcutaneous adipose tissue with the tumor extending to the resected margin. A subsequent PET scan showed a focal hypermetabolic 8-cm nodular density in the right labium majora extending into the subcutaneous tissue, without evidence of metastatic disease. The patient underwent a radical wide local excision, allowing for a 2-cm margin circumferentially. This essentially resulted in a right hemivulvectomy. She underwent a right sentinel inguinal-node dissection. On final pathology, the vulva showed no residual tumor with negative margins. Two right sentinel inguinal lymph nodes were sampled and were negative for metastatic disease. Receptor analysis of the original biopsy specimen showed strong ER- and PR-positivity.
Adjuvant hormonal therapy was initiated with 20 mg of tamoxifen p.o. q.d. Three years after surgery, this patient is alive and well, without clinical evidence of disease.
Discussion
A systematic review of the literature was performed, utilizing the PubMed search terms
Y, yes; N, no; 5-FU, 5-fluorouracil; MTX, methotrexate; IMRT, intensity modulated radiation therapy; CAF, cyclophosphamide, doxorubicin (Adriamycin) & 5-FU combined; NED, no evidence of disease.
Based on a review of the literature, it was decided to treat the three patients reported here by melding published evidence-based guidelines developed for carcinoma of the vulva and those for adenocarcinoma of the breast. The patients were treated by a multidisciplinary team in a prospective manner, with all cases presented at the breast and gynecologic tumor boards at St. Peter's Hospital. Surgery was tailored to each individual patient and consisted of radical excision, allowing for a 2-cm margin around each lesion. Unfortunately, because of anatomical considerations in these postmenopausal women, this necessitated hemivulvectomy. Sentinel inguinal lymph-node biopsies were attempted in these three patients and were successful in two patients. The third patient had negative results, probably because of nodal replacement by metastatic adenocarcinoma. The aim was to provide surgery similar in scope to breast lumpectomy and sentinel-node biopsy per breast-cancer guidelines. However, unlike the breast, given the limited tissues of the vulvas in these postmenopausal women, a 1.5–2-cm margin around the lesions and in the subcutaneous tissue required radical hemivulvectomies. All patients tolerated their surgeries without complications.
Postoperatively, all three patients were seen by medical oncology and radiation oncology specialists at St. Peter's Hospital's Cancer Care Center, in Albany NY. Based on each patient's the individual pathology, further adjuvant chemotherapy was selected, using published guidelines for adenocarcinoma of the breast, and was directed by medical oncologists. The patients were treated with combination chemotherapy as detailed above. Tamoxifen adjuvant hormonal therapy was given for patients with receptor positivity.
Radiation therapy fields were tailored based on the pathologic findings, treating the tumor beds as necessary and treating affected nodal areas. This was in keeping with published guidelines for breast cancer. Radiation therapy was tolerated well without undue side-effects. All patients are alive and well both three and four years post treatment.
Conclusions
Adenocarcinoma of the vulva arising in ectopic mammary tissue is exceedingly rare making consensus on treatment difficult. This report is about three patients who were treated by a multidisciplinary team consisting of gynecologic, medical, and radiation oncology specialists. Immunohistochemistry of these patients was identical to that seen in primary adenocarcinoma of the breast. The clinical presentation and metastatic pattern seen in these patients appeared to parallel those of adenocarcinoma of the breast. Treating these patients with established guidelines for breast carcinoma appeared to be a rational approach and was successful in the patients presented in this article.
Footnotes
Acknowledgments
The authors would like to acknowledge Duncan Savage, MD, in the department of radiation oncology at St. Peter's Hospital, Albany, NY.
Author Disclosure Statement
Neither of the authors have a conflict of interest.