|Ahead of print publication
Lobular carcinoma of the breast with metastasis to the uterine cervix
Danilo Rafael Silva Fontinele1, Sabas Carlos Vieira2, Raimundo Gerônimo da Silva Júnior3, Tatyanne Silva Rodrigues4
1 Academic of Medicine of the State University of Piauí - UESPI, Teresina, Piauí, Brazil
2 Department of Oncology, Federal University of Piaui, Teresina, Piauí, Brazil
3 Laboratory LAPAC, Brazilian Society of Pathology, Teresina, Piauí, Brazil
4 Department of Nursing, Federal University of Piauí, Teresina, Piauí, Brazil
Danilo Rafael Silva Fontinele,
Rua Galvão, 522, São João, Teresina, Piauí
Source of Support: None, Conflict of Interest: None
Metastases may occur in early-stage or locally-advanced tumors in diverse locations. Nevertheless, the uterine cervix is an uncommon site for metastasis, since the majority of tumors in this organ is primary carcinomas or result from the direct extension of primary pelvic tumors. The objective of the current study was to report a clinical case considered rare in the literature, as well as discuss its implications and peculiarities. This case report describes a 57-year-old patient with lobular carcinoma metastatic to the uterine cervix, >3 years after the termination of the left breast cancer treatment. A literature analysis confirmed that most cases presented with vaginal bleeding or abdominal discomfort, but many were asymptomatic. Common characteristics between the cases werethe patient's age, the time period between primary tumor diagnosis and the emergence of metastatic lesions, treatment, medication, and signs/symptoms. Although rare, metastasis should be considered in women with a history of breast cancer, particularly when the complaint is abnormal vaginal bleeding.
Keywords: Breast neoplasms, tumor metastasis, uterine cervix
| > Introduction|| |
Breast cancer is the most common malignancy in women. More than one million breast cancer cases are diagnosed per year, and it is one of the major causes of cancer death. The most common metastatic sites include the bones, lungs, lymph nodes, liver, and brain., The uterine cervix is a relatively uncommon site for metastasis. The majority of cervical tumors are primary carcinomas or result from a direct extension of primary pelvic tumors. We present a case of lobular breast carcinoma metastatic to the uterine cervix, >3 years after the end of breast cancer treatment.
| > Case Report|| |
A 57-year-old female sex, black race patient was diagnosed with Grade-2 lobular carcinoma of the left breast 3 years ago, measuring 10 cm in the largest tumor diameter, with edema of the skin, and clinically positive axilla. There was no blood or lymphatic invasion (T4bN1MO– stage IIIB). Immunohistochemistry (IHC) revealed that the tumor was estrogen-receptor positive (80%), progesterone-receptor positive (90%), human epidermal growth factor receptor-2 (HER-2-receptor) negative (0), ki-67 (20%); and E-cadherin-negative. Neoadjuvant chemotherapy with four cycles of doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 was initiated, followed by 12 weekly doses of paclitaxel 80 mg/m2. Complete response in the axilla and a partial response in the breast were obtained, with persistent edema. After neoadjuvant chemotherapy, the patient underwent a left modified radical mastectomy and axillary emptying. She chose not to have the breast reconstruction. In the final histopathological analysis, there was pathologic complete response in the breast, and nine axillary lymph nodes showed no metastasis. She received the radio-adjuvant therapy to the chest wall and lymphatic drainage chains. Adjuvant treatment with tamoxifen 20 mg/day was initiated and annual follow-up with mammography. After 39 months of treatment, the patient had abnormal uterine bleeding. On clinical examination, the cervix was indurated but lacked any visible tumor. Shiller test was negative. On cytology and cervical biopsy, a low-grade intraepithelial lesion was confirmed, and the patient follow-up was recommended. On transvaginal ultrasound, endometrial thickness was 3.0 mm. At 10 months after the first cervical biopsy was performed, the patient exhibited an indurated and bleeding uterine cervix and an iodine-negative area on the posterior lip during physical examination with the collection of cervical cytology samples. The iodine-negative area was completely resected. On pathology analysis [Figure 1] and [Figure 2], it was shown that the sample was compatible with metastatic breast carcinoma, which was confirmed by immunohistochemical study. H and E staining showed that the cervix was infiltrated by an epithelioid cell neoplasm. On IHC, the tumor was cytokeratin-positive, cadherin-negative, BRST-2 negative, estrogen receptor-positive (60%), progesterone receptor-positive (10%), and HER-2-negative. On chest tomography, unspecific pulmonary nodes were observed. Abdominal tomography revealed multiple sclerotic intraspongeous lesions at the levels of T11–T12 vertebrae, lumbar vertebrae, and the hip bone, which were compatible with the degenerative alterations. Computed tomography-scans of the breast, pelvic organs, and uterine cervix showed no lesions or alterations. Bone scintigraphy was normal. Anastrozole was initiated, and the patient underwent laparoscopic hysterectomy with salpingo-oophorectomy for local control due to transvaginal bleeding. Histopathology study confirmed the infiltration of the uterine cervix by carcinoma [Figure 3], without angiolymphatic or perineural invasion. The tumor infiltrated the uterine body, with no evidence of disease in the endometrium, ovaries, fallopian tubes, and parametria. Margins were clear. Surgical specimen was consistent with metastatic lobular carcinoma of the breast. Hospital discharge of the patient occurred on the 1st postoperative day. Seventeen months after surgery, she remains asymptomatic, showing no clinical evidence of disease progression.
|Figure 1: Histologic sections reveal fragments of uterine cervix infiltrated by malignant tumor with blocks and strips of uniform cells among the typical endocervical glands (H and E, ×50)|
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|Figure 2: Detail of cell infiltration in the cervical stroma (H and E, ×100)|
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|Figure 3: Specimen of laparoscopic hysterectomy with tumor infiltrating the uterine cervix|
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| > Discussion|| |
In an analysis of 325 cases of patients with metastasis to the female genital tract, the ovary and vagina were the most commonly affected sites. In a study of 52 breast cancer cases with metastasis to gynecologic organs, it was shown that the ovaries were affected in 88.5% of cases. Metastasis to the vagina occurred in 5.8%, the endometrium in 3.8%, and the vulva in 1.9%. The uterine cervix was not affected in any of the cases.
Another study conducted in women with metastasis to the uterine cervix, showed that the breast carcinoma metastatic to the uterine cervix occurred in 0.8%–1.7% of cases. Until the present, approximately 35 cases of breast cancer metastatic to the uterine cervix have been reported in the literature [Table 1]. In most cases, the primary tumor was diagnosed before the metastasis.
The uterine cervix is, therefore, an uncommon site for breast cancer metastasis. Reasons for this include small cervical size, reduced blood flow, and distal circulation, as well as abundant fibrous tissue. It is worth mentioning that metastasis to the female reproductive system in an invasive lobular carcinoma is more common than in invasive ductal carcinoma, accounting for over 80% of breast cancers that spread to the female genital organs. Nevertheless, the prognosis is the same for both types of breast cancer.
According to the literature, the shortest and longest time intervals for the appearance of metastasis were 24 months and 180 months, respectively [Table 1]. In the case presented, the time between primary cancer treatment and the appearance of abnormal uterine bleeding was 39 months. Metastatic disease induces fibrous proliferation and inflammatory cell reaction in the uterine cervix, which explains the indurated uterine cervix observed in this report.
The distinction between metastatic and primary carcinoma is crucial for the therapeutic definition. However, differentiation can be quite difficult due to various reasons: nonspecific symptoms at presentation, a long-disease-free interval, and inconclusive radiologic, and imaging and histopathological findings.
In the majority of cases, the metastatic disease manifests itself as vaginal bleeding and abdominal discomfort. However, patients can be frequently asymptomatic, and the tumor is only found during an autopsy. Presentation of metastasis, in this case, is similar to other reports in the literature.
IHC is crucial for differentiating primary cervical malignancy from the metastatic cervical malignancy. For differentiation, the following markers can be analyzed: CK7/CK20, gross cystic disease fluid protein-15, p53, p16, vimentin, BCL2, p63, and napsin A. Not all, these markers were analyzed in the current case. Nevertheless, they are important in the differential diagnosis.
A low-grade invasive lobular carcinoma with estrogen-positive receptors at the time of diagnosis is considered to have a favorable prognosis. In general, patients have a poor prognosis. However, some may obtain complete response, as in this case, and remain disease-free for prolonged periods of time, even exceeding 20 years.
Lobular breast carcinoma is usually confined to the terminal lobules. These tumors are less cohesive than ductal tumors due to the loss of E-cadherin expression and less responsive to neoadjuvant chemotherapy than ductal tumors. In a combined analysis of over 1000 patients with lobular carcinoma, pathologic complete response rate was 6.2% versus 17.4% in patients with ductal carcinoma. Thus, pathologic complete response, although uncommon, may occur, as shown in the present report.,
In the current case, the disease was limited to the uterine cervix. The patient was managed with hysterectomy for local disease control and hormone therapy with anastrozole.
| > Conclusion|| |
Metastasis to the uterine cervix should be considered in women with a history of breast cancer, especially when they exhibit abnormal vaginal bleeding.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understand that names and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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