Cutaneous metastasis of occult breast cancer: a case report

Occult breast cancer (OBC) is characterized by metastatic presentation of undetectable breast tumor on imaging exams. OBC is a rare disease (accounting for 0.3% to 1.0% of all breast cancers) that represents a major diagnostic challenge. The aim of this study was to report a case of OBC with primary presentation of multiple cutaneous metastases with subsequent emergence of bone metastasis. A 70-year female patient had multiple cutaneous metastatic lesions in the left cervical region, left breast, left axillary region, left subscapular region, in three chirodactylus of the right hand and three chirodactylus of the left hand. Imaging tests (mammogram, ultrasonography and magnetic resonance imaging of the breast) did not show alterations. Biopsy, histology sections and immunohistochemistry of the left cervical cutaneous lesion were compatible with OBC. After two years of anastrozole treatment (1mg/day), there was regression of all cutaneous lesions and stabilization of bone metastasis. OBC has a better prognosis. It may exhibit spontaneous regression or respond to less aggressive treatment strategies, as described in this case.


Introduction
Occult breast cancer (OBC) is defined as the clinical presentation of metastatic carcinoma (mainly in axillary lymph nodes) derived from a malignant primary breast tumor that is undetectable by clinical exams and radiological evaluation. OBC is a rare condition, accounting for 0.3%-1.0% of all breast cancers. It occurs most commonly at around 55 years of age [1,2]. Cutaneous metastases may be considered rare dermatological manifestations that occur in around 0.7% to 0.9% of cancer patients. Therefore, advanced breast cancer is implied in the occurrence of cutaneous metastases in cancers in general [3]. OBC represents a diagnostic challenge and is a rare event, especially with primary manifestations of systemic metastasis. Therefore, the aim of this study was to report a case of OBC, mainly manifested as cutaneous metastases and subsequent detection of bone metastasis.

Patient and observation
Patient information: a 70-year old female patient, G1P0A0, non-smoker, non-alcoholic, hypertensive and sedentary. Mammography, ultrasonography and magnetic resonance imaging of the breast were performed. No structural alterations were found in any of these exams. Chest and abdominal CT-scans did not demonstrate metastasis. The patient did not perform PET-CT due to unavailability of the exam. A bone scintigraphy showed areas of increased uptake in the 8th and 9th right costal arcs that were suspected of metastatic disease. A new scintigraphy indicated stabilization of the bone uptake detected.
Diagnosis: the results were consistent with breast cancer metastases. A diagnosis of lobular breast carcinoma of unrecognized primary site (OBC) with cutaneous metastatic dissemination was made. The first bone scintigraphy showed areas of increased uptake in the 8 th and 9 th right costal arcs suspicious for metastatic disease.
Follow-up and outcome of interventions: the patient had an excellent response to anastrozole. She remains asymptomatic and in excellent clinical condition.
Patient perspective: "I have an expectation of being cured of cancer, given that some conditions have completely disappeared and I continue with treatment and clinical follow-up".
Informed consent: the current study is part of a scientific project that was approved by the research ethics committee (REC) of the State University of Piauí, Teresina, PI, Brazil, under number CAAE: 30154720.0.0000.5209. All ethical principles established by the National Health Council resolution number 466/12 and international documents were followed. The patient gave informed consent.

Discussion
OBC is a rare and challenging diagnosis. In the literature, there is a paucity of conclusive studies on the clinical-pathological characteristics of the disease, as well as patient outcome and disease management. Huang et al. analyzed 572 OBC patients in comparison to 117.217 cases of nonoccult breast cancer. Those authors also concluded that OBC patients are diagnosed at a more advanced age, as occurred in the case report [4].
Cutaneous metastases due to breast cancer are uncommon, indicating that internal malignancies occur [3]. The first manifestation of OBC is axillary node involvement. Primary occurrence of distant metastasis is less common [5]. In the patient described, multiple cutaneous metastases were the early manifestations of OBC with subsequent detection of probable bone metastasis. Imaging techniques currently used for diagnosis of breast cancer (mammography, ultrasonography and magnetic resonance imaging) are not sensitive for OBC [6]. Nevertheless, immunohistochemical analysis of nodal or systemic presentations, with the characteristic markers of breast carcinomas, such as CK7, estrogen and progesterone receptors and GATA-3, can determine that the breast is the primary site of cancer [7].
Furthermore, OBC has a better prognosis [4,8]. In the English literature, a case of spontaneous regression (partial or total disappearance of cancer without any type of treatment) of nodal metastasis in OBC was reported [9]. In this case report, the patient with OBC had a good clinical outcome. Regression of cutaneous metastasis and stability of bone metastasis occurred, and anastrazole alone was used for treatment.
We identified three articles reporting cases of cutaneous metastasis of OBC by using the following search strategy on PubMed: "skin AND occult AND metastasis AND breast AND cancer" [3,10,11] ( Table 1). In the three other cases identified in PubMed, patients had a more aggressive disease than the patient described in this case report, requiring more robust treatment strategies, such as mastectomy, chemotherapy and radiotherapy. Therefore, this case report is quite interesting and rare. In addition, it may be considered unique in relation to the clinical outcome presented.

Conclusion
OBC has a better prognosis, with possibility of spontaneous tumor regression or response to less aggressive treatment strategies. At two years of follow-up, the patient in this case report had an excellent clinical outcome, with regression of all cutaneous metastatic lesions. Bone metastasis was stable with the sole use of anastrozole (1mg/day) for treatment.   Patient was referred to chemotherapy and clinical follow-up, but died soon afterwards (10 months after diagnosis). Cohen-Kurzrock et al. [11] 2021 30-year old woman with cutaneous metastasis in the breasts, axillary region and groin.

Table and figures
Not detailed. Mastectomy of the right breast and adjuvant chemotherapy. Patient under chemotherapy at the time of case publication.