Incidental detection of rare metastatic basal cell carcinoma on screening mammography

Abstract

Basal cell carcinoma (BCC) is the most common nonmelanoma skin cancer but rarely metastasizes, with an estimated metastatic rate of 0.1%. Metastatic spread to axillary lymph nodes is extremely uncommon, and to our knowledge, no prior cases have reported incidental detection on screening mammography. We report the case of a 48-year-old Caucasian female with a history of renal transplants, chronic immunosuppression, and multiple biopsy-confirmed BCCs and cutaneous squamous cell carcinomas who presented with a new axillary mass incidentally found on screening mammography. Final pathology following axillary lymph node dissection revealed metastatic BCC.

This case illustrates the diagnostic complexity of axillary masses found on screening mammography and underscores the need for vigilant evaluation of BCC metastases in immunosuppressed patients. It highlights the diagnostic limitations of imaging and core biopsy in distinguishing BCC from cutaneous squamous cell carcinomas or metastatic breast carcinoma. Given the poor prognosis of metastatic BCC, this report supports more proactive imaging strategies in high-risk individuals and emphasizes the need for further research into optimal management.

Introduction

Basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC) account for over 90% of cutaneous malignancies [1]. It is estimated that 5.4 million patients are diagnosed with nonmelanoma skin cancer (NMSC) in the United States yearly, with approximately 80% being BCCs and 20% being cSCCs [2]. While BCC and cSCC are both common, they rarely metastasize; the risk of metastasis for BCC and cSCC is up to 0.1% and 7%, respectively [[3], [4]]. In contrast, invasive melanoma accounts for 1% of all skin cancers but the majority of skin cancer deaths [5].

The lungs, liver, and bone are the most frequent sites of distant metastases in BCC and cSCC [6,7]. Metastasis to regional lymph nodes represents 50% and 87% of all BCC and cSCC metastases, respectively, with the cervical nodes predominantly affected in both BCC and cSCC [6,7]. BCC and cSCC axillary nodal metastases have been rarely reported, often detected on physical exam [[8], [9], [10], [11], [12], [13], [14], [15]].

To our knowledge, there are no studies that describe the detection of BCC axillary metastasis on asymptomatic screening mammography. Here we present a case of a female with a history of renal transplants and multiple NMSCs incidentally found to have metastatic BCC on a screening mammogram. This case highlights radiologic and pathologic diagnostic considerations as well as management in high-risk patients, such as the immunosuppressed.

Case presentation

A 48-year-old Caucasian female with a history Stage IV kidney failure due to reflux nephropathy status post 4 kidney transplants between ages of 11 and 40 years presented to the dermatology clinic with multiple verrucous growths. Some of these lesions represented biopsy confirmed cases of cSCC and BCC. The most recent case occurring on her left dorsolateral forearm at age 48 was confirmed to be invasive cSCC treated with Mohs surgery (Fig. 1). She also had a total of 3 cases of BCC on her bilateral shoulders and left upper back, two of which were removed via Mohs surgery and one of which was removed by wide local excision (Fig. 2). The margins were clear for all of these procedures.

Fig. 1.

(A) Left dorsolateral forearm firm pink papule with central hyperkeratosis, confirmed to be invasive SCC on shave biopsy. (B) Mohs surgery was performed. (C) Primary closure followed surgery. Negative surgical margins were obtained.

Fig. 2.

(A) Left upper back erythematous scaling plaque with scabbing, confirmed to be nodular and focally invasive BCC on shave biopsy. (B) Mohs surgery was performed with primary closure. Negative surgical margins were obtained.

Her skin cancer risk factors included immunosuppression, White race, and a family history of melanoma. Due to multiple renal transplants, she had been on various immunosuppressant regimens over the years. At one point, cyclosporine and mycophenolate mofetil were discontinued due to risk of skin cancer. She was also prescribed Acitretin, nicotinamide, and 5-fluorouracil to decrease the risk of skin cancer and for treatment of actinic keratoses.

At age 48, a routine screening mammogram demonstrated a new high density irregular mass in the left axilla (Fig. 3A). On diagnostic evaluation, targeted ultrasound showed a corresponding 1.5 cm irregular mass with indistinct margins in the left axilla designated as BI-RADS 4, suspicious (Fig. 3B). There was otherwise no mammographic abnormality in either breast.

Fig. 3.

(A) Screening mammogram demonstrated a new high density irregular mass in the left axilla on MLO view (circle). (B) Targeted ultrasound demonstrated a corresponding 1.5 cm irregular hypoechoic mass with loss of fatty hilum, indistinct margins, and internal vascularity in the left axilla prompting ultrasound biopsy.

The patient underwent an ultrasound-guided core needle biopsy of this mass. Biopsy pathology demonstrated invasive carcinoma involving fibroadipose tissue positive for p40 and Ber-EP4, suggestive of metastatic basal cell carcinoma or squamous cell carcinoma with basaloid features. The biopsy specimen was negative for estrogen receptor and SOX-10, making breast carcinoma and melanoma less likely.

PET/CT demonstrated a corresponding intensely hypermetabolic left axillary mass, consistent with the biopsy-proven invasive carcinoma (Fig. 4). No other discrete lesions with increased FDG uptake were found. Breast MRI was deferred given the patient’s renal transplant history and risk of gadolinium-induced nephrotoxicity, as well as suspicion of a non-breast primary malignancy based on the biopsy specimen immunophenotype.

Fig. 4.

Full body PET/CT demonstrated a hypermetabolic left axillary mass consistent with the biopsy-proven invasive carcinoma (arrow).

The patient subsequently underwent a left axillary node dissection. Surgical pathology revealed metastatic basal cell carcinoma involving 4 out of 26 lymph nodes, including extranodal extension and tumor within extranodal lymphatics (Fig. 5). Given extranodal regional metastatic disease, adjuvant radiation was recommended following surgery.

Fig. 5.

Surgical histopathology demonstrated invasive carcinoma involving fibroadipose tissue. (A) Hematoxylin and eosin-stained invasive carcinoma (100x). (B) Ber-EP4 immunohistochemical stain with membranous positivity in the carcinoma, suggestive of metastatic basal cell carcinoma (100x).

Discussion

Metastatic BCC is exceedingly rare, with an estimated incidence of up to 0.1% [3]. Given its rarity, metastatic BCC can present with diagnostic challenges, especially in immunosuppressed patients who are at high risk for multiple skin malignancies. This case highlights the complexities of diagnosing metastatic BCC to the axillary lymph nodes, which, to our knowledge, has never been reported as incidentally detected on screening mammography.

On imaging, increased nodal size and density, irregular shape, and loss of the fatty hilum are indicators of axillary nodal abnormality. The most common source of axillary nodal metastases is from an ipsilateral known primary breast carcinoma. Approximately 1% of breast cancers can present with axillary metastases in the absence of a known primary breast tumor [16]. The most common non-mammary axillary nodal malignancies include lymphoma or metastases from primary lung carcinoma, ovarian carcinoma, melanoma, or sarcoma, with metastatic BCC and cSCC rarely described [[8], [9], [10], [11], [12], [13], [14], [15],17].

This case demonstrates potential diagnostic challenges that can arise after a core biopsy. The biopsy specimen alone could not differentiate between metastatic BCC and cSCC with basaloid features in this patient with a history of multiple prior NMSCs. BCCs and cSCCs with basaloid features as well as basal-like, triple negative, and metaplastic breast carcinomas are histologically similar, but immunophenotypes can help differentiate them. BCC typically stains positive for Ber-EP4 and negative for p40. However, both were positive in this case and therefore could not reliably differentiate between BCC and basaloid cSCC on core biopsy. Estrogen/progesterone receptor positivity would have suggested a breast primary and SOX-10 positivity would have suggested a melanoma primary, both of which were not seen in this case. Surgical excision was needed for a definitive diagnosis.

Current guidelines on the evaluation for metastatic BCC are lacking due to its low metastatic potential and therefore rare occurrence. Patients with BCC should receive a history and physical examination including complete skin examination every 6-12 months for the first 5 years following diagnosis, then at least annually for life [18]. Imaging is not recommended for asymptomatic patients without high-risk features of BCC. The National Comprehensive Cancer Network (NCCN) defines high risk features as large lesions, recurrence, perineural or vascular invasion, deep invasion into extradermal structures, location in the centrofacial area, aggressive histologic subtype, and immunosuppression [18]. CT, PET/CT, MRI, or ultrasound may be considered in patients with high-risk BCC [19]. Our patient had many of these features, including invasive subtype on shave biopsy, immunosuppression, and prior NMSC recurrences, but she did not receive any baseline imaging to evaluate for metastases.

While sentinel lymph node biopsy is used in melanoma to detect nodal metastases in the absence of palpable lymphadenopathy, there is insufficient evidence for its use to detect subclinical nodal metastases in BCC and cSCC [20]. Because palpation has a false-negative rate of 15%-30% for detecting nodal metastasis, imaging may be considered for high-risk BCC or cSCC even in the absence of palpable nodes [21,22].

Our patient’s immunosuppression following multiple kidney transplants placed her at significantly increased risk for developing NMSCs. Risk of skin cancer in organ transplant recipients is 65-250 fold higher than the general population for cSCC, 10-16 fold higher for BCC, and 3 fold higher for melanoma [23,24]. Risk factors for post-transplant skin cancer include older age at transplant, Caucasian race, male sex, post-transplant precancerous skin lesions, and higher duration and dosage of immunosuppressive therapy [25,26]. BCC in the setting of immunosuppression is deemed high-risk according to the 2025 NCCN guidelines [18].

Prognosis in metastatic BCC is poor, especially in the presence of distant metastases [3,27]. The time between primary BCC diagnosis and metastasis tends to be long, with a median of 9 years, as seen with our patient who was diagnosed with metastatic disease approximately 6 years after initial BCC diagnosis [28]. Median survival time after diagnosis of metastatic BCC has been reported to be between 10 months and 7.3 years for metastatic BCC [28].

The treatment of metastatic BCC has evolved significantly with the introduction of Hedgehog pathway inhibitors, such as vismodegib and sonedegib, and immune checkpoint inhibitors, such as cemiplimab-rwlc [18,29,30]. The NCCN recommends the use of these agents in certain situations of locally advanced, nodal, or distant metastatic BCC not amenable to curative surgery or radiation therapy [18]. The American Society of Radiation Oncology recommends curative radiation in certain patients who are not surgical candidates, and postoperative regional radiation for patients in which the risk of recurrence is high [31].

This rare case represents a diagnostically challenging presentation of metastatic BCC to the axillary lymph nodes, incidentally found on screening mammography. The lack of standardized imaging guidelines for high-risk BCC complicates early detection of metastases. This case supports the consideration of baseline and surveillance imaging in patients with multiple high-risk features of BCC, even in the absence of symptoms. The case also underscores the limitations of imaging and core biopsy in diagnosing axillary masses, emphasizing the role of immunohistochemical markers in distinguishing BCC from cSCC or aggressive breast carcinoma. Finally, it contributes to the limited literature on managing nodal metastases in BCC and calls for further research on optimal treatment strategies.

Patient consent

The authors certify that written, informed consent for publication of this case report was obtained from the patient.