A case of basal cell carcinoma of skin with bone metastasis: a case report

Abstract

Background

Basal cell carcinoma is the most prevalent skin cancer, most characterized by local aggressiveness but with low metastatic potential, and bone metastasis is quite heterogeneous, thus the incidence profile is variable size from 0.0028% to 0.5%. We have this patient with an unusual example of basal cell carcinoma with bone metastases to add to the scarce report on this matter.

Case description

Here we document a 48-year-old Persian man with a background of being exposed to the sun for a long time. He was diagnosed with an ulcer on the cheek, which was clinically characterized and further confirmed by biopsy as morpheaform basal cell carcinoma. Following the first round of excision, multiple relapses eventually metastasized to the bone. The latter was found on follow-up radiologic scans. This case is characterized by the aggressive nature of the disease and the heterogeneity of basal cell carcinoma growth, thus challenging the conventional view of basal cell carcinoma behavior. Treatment included surgical excision of the primary lesion, which was treated with radiotherapy afterward. However, the skeleton improved slowly during follow-up, and palliative care was eventually pursued to control symptoms and improve quality of life.

Conclusions

This was a rare case of basal cell carcinoma metastasis to non-bone organs, which reminded us to consider basal cell carcinoma metastasis, especially in the case of atypical basal cell carcinoma. Therefore, risk-aware patient management is essential. Moreover, these findings highlight the role of further research into the mechanisms of basal cell carcinoma metastasis, leading to improved therapeutic strategies that may lead to potential improvements in patient outcomes.

Introduction

Basal cell carcinoma (BCC) is the most frequent nonmelanoma skin cancer, occurring primarily in the elderly, with an estimated incidence of approximately 3 million Americans per year, among all nonmelanoma skin cancers about 80%, making it a public health parable. BCC rates increased dramatically and nearly doubled from 1976–1984 to 2000–2010 [1]. There were significant interactions between family history of melanoma and number of blistering sunburns between age 15-20 years on BCC risk; similarly, sunburn reactions during either childhood or adolescence had a significant interaction with SCC risk [2]. The burden of cancer is not only medical but also financial; the annual cost of nonmelanoma skin cancer treatment in the USA is estimated at $4.8 billion. This economic crisis justifies adopting effective measures to manage this prevalent disease [3, 4]. Furthermore, although BCC usually carries a low risk of metastasis, several subtypes of BCC, including infiltrative, morphiform, micronodular, and metatypical, show an aggressive and metastatic clinical course and require early detection of malignant growth as well as treatment options. This report describes the presentation, diagnosis, and management of a patient with BCC who had extremely unusual distant bone metastases. It is the subject of BCC-causing extremely high-risk features. Further, this discussion opens to factors that contribute to BCC metastasis, including early intervention, and describes the necessity for comprehensive differential diagnosis to diagnose the metastasis early and maximize treatment and efficacy.

Case presentation

A 48-year-old Persian male patient, who was a heavy smoker with a medical history of type 2 diabetes and hypertension, but no psychiatric history or family history of cancer, presented with persistent lesions on his left cheek. He was an interested outsider exposed to ultraviolet rays. Cutaneous basal cell carcinoma (BCC) was diagnosed. Physical examination revealed a 2.0 × 1.5 × 1.2 cm mass. Initial skin histopathology showed that morpheaform BCC affects the skin and cutaneous tissues. He initially underwent surgery to remove the tumor but received no radiotherapy.

In December 2021, he visited our institution because of bone pain and wound deterioration. On admission, a large lesion measuring 8.5 × 10 cm and 5.5 cm deep was revealed on the left cheek (Fig. 1).

Fig. 1

Clinical image of the patient’s ulcer, noted on presentation and measuring 8.5 × 10 cm with a depth of 5.5 cm

After consultation with an oncologist, dermatologist, and orthopedic surgeon, a bone biopsy suddenly revealed metastatic basal cell carcinoma (mBCC) in the bones, and a computed tomography (CT) scan of the face and spinal cord was three-dimensionally (3D) reconstructed and without any differentiation, including adjacent to his left maxillary sinus, especially at the left lower border defect, and lytic lesions with sclerotic borderline in the pelvic ramus. (Figs. 2, 3). The remainder of the examined area was unremarkable. Subsequent investigations, including bone scans, revealed extensive bone metastasis involving the spine, shoulders, ribs, and pelvis.

Fig. 2

Computed tomography of face with 3D reconstruction and without contrast showing a defect in the left facial area adjacent to the left maxillary sinus with evidence of the defect in the left inferior border of the maxillary sinus (blue arrow)

Fig. 3

Computed tomography scan of the pelvis showing lytic lesions with sclerotic borders in pelvis bone (blue arrows)

Histologically, the primary lesion showed the strands and islands of basaloid cells embedded within a dense, sclerotic stroma. It displayed minimal cytologic atypia, and the growth pattern was highly infiltrative with hardly clear margins (Fig. 4).

Fig. 4

Histopathology of the lesion at the time of bone metastasis diagnosis

The metastatic lesions of the bone showed invasive islands and strands of basaloid cells within the bone marrow. These cells disrupt the normal marrow architecture, potentially impacting hematopoiesis by replacing the marrow space.

Histologically, the bone itself may show evidence of osteolytic damage where the tumor has eroded bone tissue. This results in areas of decreased bone density, characterized by loss of normal bone trabeculae and infiltration by malignant cells. The interface between the tumor and normal bone might not be demarcated, with tumor cells invading in a diffuse pattern that makes surgical margins difficult to determine (Fig. 5).

Fig. 5

Histopathology of the metastatic lesion to bone (pelvis), bone marrow penetrated by irregular clusters of malignant tumor tissue

We started palliative radiotherapy in the painful regions with palliative systemic chemotherapy consisting of cisplatin 100 mg, 5-fluorouracil 2 g, and zoledronic acid 4 mg per month. He had some symptom reduction at that time, but his left facial lesion was the same. He was still followed up in our oncology department and was clinically stable, without progression or evidence of any new lesion on cisplatin, fluorouracil, or zoledronic acid.

Discussion

As the most prevalent cancer in the USA, basal cell carcinoma is the most frequent non melanocytic skin cancer (NMSC); thus its prevalence relative to the population of all other diseases, in addition to the approximately 1 million new cases of BCC being administered in the USA yearly, warrants it as the top disease. Approximately 3000 patients die every year [5,6,7]. Despite its high frequency, mBCC is rare. We presented a case where cutaneous BCC metastasized to bone at a distant site. The case of such patients shall always indicate the necessity for multiple differential distinctions due to which all clinical settings must provide early detection and management to all the cases.

There has been great advancement in the management of SCC and BCC in the USA over the past 20 years, particularly in women less than 40 years of age, due to increased aging population, changes in sun exposure habits, environmental shifts, migratory patterns, and increased use of immunosuppressants [5]. BCC is normally diagnosed early and generally manageable, but there has been a marked rise in the number of reported patients of mBCC between 1981 and 2011, an indication of an increase in overall BCC cases. Wysong et al. reviewed all cases of mBCC in 2013 and updated the previous case reports [7, 8].

As the most common cancer in the USA, basal cell carcinoma is the most common NMSC, hence the highest disease in prevalence relative to the population of all the other cancers combined with approximately 1 million new cases of BCC in the USA annually. Approximately 3000 people die each year [7]. Despite its high prevalence, metastatic BCC is rare. This paper described a patient with a very rare condition: cutaneous BCC that metastasized to bone at a distant site. Such cases will always indicate having multiple differential diagnoses in clinical settings to facilitate early diagnosis and management.

While BCC is normally early detectable and manageable, there was a remarkable rise of reported mBCC cases between 1981 and 2011, indicating an overall rise in BCC cases. In 2013 Wysong et al. reviewed all cases of mBCC and updated previous reports of cases [7, 8].

A retrospective review of all MBCC cases published by Wysong et al. [7] reported 194 new cases, thereby making a total of 364 cases from 1894 to 2011. Additionally, most of the tumors are large tumors in white adult male patients, and were predominantly located in the head and neck and occurred more frequently with lymph node dissemination (Table 1). Cancer size and late treatment were important prognostic factors, and those diagnosed later had poor outcomes. Over the past three decades, 44% of patients received treatment as helpful as chemotherapy or radiation without significant improvement in survival rates. These reported data may serve as an important starting point for evaluating emerging therapies, including vismodegib and other sonic hedgehog inhibitors (sHHIs), which may offer new prospects for improving survival in patients with mBCC.

Table 1 Characteristics of metastatic basal cell carcinoma cases (7)

Most basal cell carcinomas are treated with surgery, such as Mohs micrographic surgery, curettage, radiation, and chemotherapy, including cisplatin-based chemotherapy and topical therapies such as 5-FU and imiquimod. Sonic hedgehog inhibitors irrespective of the molecular signature can be used as the treatment. The findings are based on the observation of abnormalities in the hedgehog signaling system (Shh). This signaling pathway was first identified in mice in the 1990s.

Further, the hedgehog pathway is appellant to sporadic forms of BCCs and an autosomal dominant genetic disorder designed as basal cell nevus syndrome BCNS or Gorlin–Goltz syndrome. The association of developmental disorders and cyclopamine found within the California corn lily was first described in the 1960s when sheep that ate the plant produced offspring with holoprosencephaly.

It was not until the 1990s that findings confirmed that these actions resulted from the consequences of cyclopamine interacting with the endogenous transmembrane protein smoothened. PTCH, a protein that acts as a receptor in the hedgehog signaling pathway, is involved in cell communication and growth and often carries mutations in differentiated basal cell carcinomas (BCCs) and basal cell nevus syndrome (BCNS) [9,10,11,12].

New sHHIs are being examined for use in the treatment of BCC. Vismodegib was the first sound hedgehog pathway inhibitor approved by the US Food and Drug Administration in 2012 for the treatment of BCC. The understanding that dysregulated hedgehog signaling is responsible for local and metastatic BCC has led to the development of new targeted therapeutics [13, 14]. Two sonic hedgehog pathway inhibitors, vismodegib and sonidegib, have thus been approved in locally advanced and metastatic BCC treatment [15, 16].

In considering BCCs in general, and particularly when basaloid morphology is evident, the pathologist must be aware of metastatic bone lesions in their differential diagnosis. In mBCC, an early diagnosis could make all the difference in treatment efficacy and significantly improve patient survival.

Conclusions

This case report highlights the rarity of metastatic basal cell carcinoma (mBCC), suggesting the possibility of aggressive progression despite the nonmetastatic nature of BCC. We highlighted the critical importance of surveillance, as well as having vast differential diagnoses to find the metastasis earlier and start the intervention, especially with the hedgehog signaling pathway, as targeted therapies such as vismodegib and sonidegib offer potential new treatments for metastatic BCC. However, observing cases with poor prognoses despite this interventional improvement highlights the need for continued research into more effective treatment strategies.