Extensive Basal Cell Carcinoma With Probable Bone Metastasis

Basal cell carcinoma (BCC) is the most common of all malignant neoplasms; approximately 1 million new cases occur annually in the United States, with increasing incidence.¹ Although BCC is locally invasive, the occurrence of BCC metastasis is exceedingly rare, with an average rate of approximately 0.03%,² typically involving a large, long-standing, locally destructive, recalcitrant tumor of the head or neck.³ BCC metastasis is rare because of the early recognition of the disease, current treatment, and the noninvasive character of the tumor. In the event of metastatic spread, the most commonly involved sites (in descending order of frequency) include regional lymph nodes, the lungs, and bone, but also may involve the pleura and abdominal viscera.⁴ Criteria used to establish the diagnosis of metastatic BCC were put forth in 1951 by Lattes and Kessler⁵ and include: (1) the neoplasm must originate from skin, not mucous membranes; (2) direct invasion of the neoplasm to the presumed metastatic site must be ruled out; and (3) primary and metastatic lesions must show identical histologic features consistent with BCC.

Bone is involved in approximately 20% to 30% of metastatic BCCs.^3,6 In addition to the above guidelines, other objective findings in BCC metastatic to bone have been reported in the literature, such as increased skeletal uptake on bone scintigraphy, elevated serum levels of alkaline phosphatase, and radiographic imaging studies that demonstrate lytic bone lesions.⁷ We report a case of BCC with probable extensive metastases to the axial skeleton above the pelvis. Results of a physical examination, as well as x-ray and bone scintigraphy findings, were consistent with extensive skeletal involvement by metastatic tumor. Histologic confirmation of bone metastasis was not possible due to the patient's family's refusal of a postmortem biopsy of the bone specimen.

Case Report

A 56-year-old white male veteran presented to a Midwestern United States veterans affairs medical center with 2 prominent skin lesions of unknown duration. The patient stated that the lesions began as small boils on his upper back and right arm many years ago and subsequently enlarged. He had not been seen by a physician for many years. Results of a physical examination revealed the patient was a cachectic man in no apparent distress; he had no fever and his vital signs were within reference range. His skin examination revealed an extensive, ulcerated, weeping lesion with rolled borders on his upper back extending to the posterior neck, and another similar lesion on his right arm. The lesion on his back measured 26X15 cm, and the lesion on his arm measured 12X6 cm (Figure 1). No mucous membrane involvement was noted. Biopsies of skin specimens were obtained from both lesions for histologic diagnosis, which confirmed the presence of BCC (Figure 2). Because of the lesions' proximity to bone, bone radiographs were performed on the patient's chest, bilateral shoulders, and right arm, revealing punched-out lytic bone lesions in the ribs, left clavicle, scapulae, and right humerus (Figure 3A). Next, a bone scintigraphy scan was performed to survey the extent of disease, revealing a "superscan," with increased bony uptake in most of the axial skeleton above the pelvis along with other discrete areas of increased uptake in the upper extremities (Figure 3B). Additional laboratory data were not available. The patient was admitted to the medical center for improvement of his nutritional status and for the management of his skin lesions. On the seventh day of hospitalization, the patient unexpectedly died, and his family refused an autopsy.

Please refer to the PDF to view the figures

Comment

The first case of BCC metastatic to a submandibular lymph node was reported by Beadles⁸ in 1894. Few cases have been described in the literature since then, and rates of metastasis have been reported to be from 0.0028% to 0.4%, depending on the study protocol used.⁹ Although histologic confirmation of bone involvement is lacking, in the absence of other detectable malignancies, our objective clinical and radiographic findings point toward bone metastasis in our patient. A review of several case reports of BCC metastatic to bone demonstrates clinical and radiographic similarities with those of our patient (Table).

Please refer to the PDF to view the table

In contrast to nonmetastatic BCC, the age of onset of metastatic lesions is approximately 45 to 59 years, with an interval of approximately 9 to 11 years between primary tumor onset and spread.¹ However, cases of metastasis have been reported after latency periods of up to 23,²⁰ 26,²¹ and even 45³ years following diagnosis of primary lesions. Men are more often affected, and tumors generally are large, long-standing, and refractory to treatment.³ No significantly different histologic characteristics in metastatic tumors were identified by Wermuth and Fajardo²²; however, other authors have concluded that metatypical BCC, or BCC with foci of squamous differentiation, demonstrates more aggressive behavior and increased potential to metastasize.^9-11,16,19 Factors noted to be associated with an increased incidence of metastasis include long duration of a large primary lesion on the head or neck,²³ recalcitrance to treatment,¹ immunodeficiency combined with stromal independence of the tumor,²⁴ inadequate excision followed by immediate wound closure,²⁵ and lesion depth.²⁶ Farmer and Helwig¹⁶ noted a paucity of inflammatory cells in the vicinity of recurrent tumors, implicating the possibility of a defective cellular immune response as a contributing factor. Our patient's evolving history, however, was unclear due to his inability to provide an accurate account.

Total excision of primary tumors following recommended treatment guidelines does not tend to halt metastatic spread,⁴ and prior to discovery of metastases, lesions generally tend to recur locally following excision and/or radiation therapy.^1,4,9 Approximately equal rates of hematogenous and lymphatic spread are observed, and the lung is the most likely distant organ to be involved, followed by bone, liver, and pleura.³ Cases of bone metastasis may present with symptoms of spinal cord compression⁶ or anemia,¹⁵ as well as bone pain¹⁷ and pathologic fractures,^7,15 and tend to involve the lumbar spine more frequently than the thoracic and cervical regions.¹⁰ Our patient did not complain of any such symptoms indicative of osseous lesions, even with extensive bony involvement.

von Domarus and Stevens³ noted a slightly better survival rate among patients with lymphatic metastases versus those patients whose tumors disseminated hematogenously. Patients with metastatic BCC have a 5-year survival rate of approximately 10%; patients with distant spread typically survive only 10 to 14 months.¹ Prognosis is especially poor with metastases to the lungs, bone, or liver,^12,16 and palliative treatment generally is used in these cases.

Aggressive treatment should be pursued if BCC metastasis has been detected. Unfortunately, once distant metastasis occurs, cure is not possible and survival generally is short.¹² Excision of the primary lesion with free margins is the initial objective, but it may not always be possible due to the size or extent of the tumor. Therapeutic options for bone metastases include chemotherapy with agents such as cyclophosphamide, etoposide, fluorouracil, methotrexate, cisplatin, bleomycin, and doxorubicin.¹¹ Radiation therapy is an effective palliative treatment, but its use has not demonstrated increased survival benefit.¹² Laminectomy has been used for vertebral involvement.^10,12 Because of the rare nature of metastatic BCC, appropriate treatment protocols have not been formulated, and combination therapy with the above modalities generally is employed. Nevertheless, therapeutic response to treatment usually is poor. Because of our patient's untimely death, no treatment options were sought. 

Basal cell carcinoma (BCC) is the most common of all malignant neoplasms; approximately 1 million new cases occur annually in the United States, with increasing incidence.¹ Although BCC is locally invasive, the occurrence of BCC metastasis is exceedingly rare, with an average rate of approximately 0.03%,² typically involving a large, long-standing, locally destructive, recalcitrant tumor of the head or neck.³ BCC metastasis is rare because of the early recognition of the disease, current treatment, and the noninvasive character of the tumor. In the event of metastatic spread, the most commonly involved sites (in descending order of frequency) include regional lymph nodes, the lungs, and bone, but also may involve the pleura and abdominal viscera.⁴ Criteria used to establish the diagnosis of metastatic BCC were put forth in 1951 by Lattes and Kessler⁵ and include: (1) the neoplasm must originate from skin, not mucous membranes; (2) direct invasion of the neoplasm to the presumed metastatic site must be ruled out; and (3) primary and metastatic lesions must show identical histologic features consistent with BCC.

Bone is involved in approximately 20% to 30% of metastatic BCCs.^3,6 In addition to the above guidelines, other objective findings in BCC metastatic to bone have been reported in the literature, such as increased skeletal uptake on bone scintigraphy, elevated serum levels of alkaline phosphatase, and radiographic imaging studies that demonstrate lytic bone lesions.⁷ We report a case of BCC with probable extensive metastases to the axial skeleton above the pelvis. Results of a physical examination, as well as x-ray and bone scintigraphy findings, were consistent with extensive skeletal involvement by metastatic tumor. Histologic confirmation of bone metastasis was not possible due to the patient's family's refusal of a postmortem biopsy of the bone specimen.

Case Report

A 56-year-old white male veteran presented to a Midwestern United States veterans affairs medical center with 2 prominent skin lesions of unknown duration. The patient stated that the lesions began as small boils on his upper back and right arm many years ago and subsequently enlarged. He had not been seen by a physician for many years. Results of a physical examination revealed the patient was a cachectic man in no apparent distress; he had no fever and his vital signs were within reference range. His skin examination revealed an extensive, ulcerated, weeping lesion with rolled borders on his upper back extending to the posterior neck, and another similar lesion on his right arm. The lesion on his back measured 26X15 cm, and the lesion on his arm measured 12X6 cm (Figure 1). No mucous membrane involvement was noted. Biopsies of skin specimens were obtained from both lesions for histologic diagnosis, which confirmed the presence of BCC (Figure 2). Because of the lesions' proximity to bone, bone radiographs were performed on the patient's chest, bilateral shoulders, and right arm, revealing punched-out lytic bone lesions in the ribs, left clavicle, scapulae, and right humerus (Figure 3A). Next, a bone scintigraphy scan was performed to survey the extent of disease, revealing a "superscan," with increased bony uptake in most of the axial skeleton above the pelvis along with other discrete areas of increased uptake in the upper extremities (Figure 3B). Additional laboratory data were not available. The patient was admitted to the medical center for improvement of his nutritional status and for the management of his skin lesions. On the seventh day of hospitalization, the patient unexpectedly died, and his family refused an autopsy.

Please refer to the PDF to view the figures

Comment

The first case of BCC metastatic to a submandibular lymph node was reported by Beadles⁸ in 1894. Few cases have been described in the literature since then, and rates of metastasis have been reported to be from 0.0028% to 0.4%, depending on the study protocol used.⁹ Although histologic confirmation of bone involvement is lacking, in the absence of other detectable malignancies, our objective clinical and radiographic findings point toward bone metastasis in our patient. A review of several case reports of BCC metastatic to bone demonstrates clinical and radiographic similarities with those of our patient (Table).

Please refer to the PDF to view the table

In contrast to nonmetastatic BCC, the age of onset of metastatic lesions is approximately 45 to 59 years, with an interval of approximately 9 to 11 years between primary tumor onset and spread.¹ However, cases of metastasis have been reported after latency periods of up to 23,²⁰ 26,²¹ and even 45³ years following diagnosis of primary lesions. Men are more often affected, and tumors generally are large, long-standing, and refractory to treatment.³ No significantly different histologic characteristics in metastatic tumors were identified by Wermuth and Fajardo²²; however, other authors have concluded that metatypical BCC, or BCC with foci of squamous differentiation, demonstrates more aggressive behavior and increased potential to metastasize.^9-11,16,19 Factors noted to be associated with an increased incidence of metastasis include long duration of a large primary lesion on the head or neck,²³ recalcitrance to treatment,¹ immunodeficiency combined with stromal independence of the tumor,²⁴ inadequate excision followed by immediate wound closure,²⁵ and lesion depth.²⁶ Farmer and Helwig¹⁶ noted a paucity of inflammatory cells in the vicinity of recurrent tumors, implicating the possibility of a defective cellular immune response as a contributing factor. Our patient's evolving history, however, was unclear due to his inability to provide an accurate account.

Total excision of primary tumors following recommended treatment guidelines does not tend to halt metastatic spread,⁴ and prior to discovery of metastases, lesions generally tend to recur locally following excision and/or radiation therapy.^1,4,9 Approximately equal rates of hematogenous and lymphatic spread are observed, and the lung is the most likely distant organ to be involved, followed by bone, liver, and pleura.³ Cases of bone metastasis may present with symptoms of spinal cord compression⁶ or anemia,¹⁵ as well as bone pain¹⁷ and pathologic fractures,^7,15 and tend to involve the lumbar spine more frequently than the thoracic and cervical regions.¹⁰ Our patient did not complain of any such symptoms indicative of osseous lesions, even with extensive bony involvement.

von Domarus and Stevens³ noted a slightly better survival rate among patients with lymphatic metastases versus those patients whose tumors disseminated hematogenously. Patients with metastatic BCC have a 5-year survival rate of approximately 10%; patients with distant spread typically survive only 10 to 14 months.¹ Prognosis is especially poor with metastases to the lungs, bone, or liver,^12,16 and palliative treatment generally is used in these cases.

Aggressive treatment should be pursued if BCC metastasis has been detected. Unfortunately, once distant metastasis occurs, cure is not possible and survival generally is short.¹² Excision of the primary lesion with free margins is the initial objective, but it may not always be possible due to the size or extent of the tumor. Therapeutic options for bone metastases include chemotherapy with agents such as cyclophosphamide, etoposide, fluorouracil, methotrexate, cisplatin, bleomycin, and doxorubicin.¹¹ Radiation therapy is an effective palliative treatment, but its use has not demonstrated increased survival benefit.¹² Laminectomy has been used for vertebral involvement.^10,12 Because of the rare nature of metastatic BCC, appropriate treatment protocols have not been formulated, and combination therapy with the above modalities generally is employed. Nevertheless, therapeutic response to treatment usually is poor. Because of our patient's untimely death, no treatment options were sought. 

Basal cell carcinoma (BCC) is the most common of all malignant neoplasms; approximately 1 million new cases occur annually in the United States, with increasing incidence.¹ Although BCC is locally invasive, the occurrence of BCC metastasis is exceedingly rare, with an average rate of approximately 0.03%,² typically involving a large, long-standing, locally destructive, recalcitrant tumor of the head or neck.³ BCC metastasis is rare because of the early recognition of the disease, current treatment, and the noninvasive character of the tumor. In the event of metastatic spread, the most commonly involved sites (in descending order of frequency) include regional lymph nodes, the lungs, and bone, but also may involve the pleura and abdominal viscera.⁴ Criteria used to establish the diagnosis of metastatic BCC were put forth in 1951 by Lattes and Kessler⁵ and include: (1) the neoplasm must originate from skin, not mucous membranes; (2) direct invasion of the neoplasm to the presumed metastatic site must be ruled out; and (3) primary and metastatic lesions must show identical histologic features consistent with BCC.

Bone is involved in approximately 20% to 30% of metastatic BCCs.^3,6 In addition to the above guidelines, other objective findings in BCC metastatic to bone have been reported in the literature, such as increased skeletal uptake on bone scintigraphy, elevated serum levels of alkaline phosphatase, and radiographic imaging studies that demonstrate lytic bone lesions.⁷ We report a case of BCC with probable extensive metastases to the axial skeleton above the pelvis. Results of a physical examination, as well as x-ray and bone scintigraphy findings, were consistent with extensive skeletal involvement by metastatic tumor. Histologic confirmation of bone metastasis was not possible due to the patient's family's refusal of a postmortem biopsy of the bone specimen.

Case Report

A 56-year-old white male veteran presented to a Midwestern United States veterans affairs medical center with 2 prominent skin lesions of unknown duration. The patient stated that the lesions began as small boils on his upper back and right arm many years ago and subsequently enlarged. He had not been seen by a physician for many years. Results of a physical examination revealed the patient was a cachectic man in no apparent distress; he had no fever and his vital signs were within reference range. His skin examination revealed an extensive, ulcerated, weeping lesion with rolled borders on his upper back extending to the posterior neck, and another similar lesion on his right arm. The lesion on his back measured 26X15 cm, and the lesion on his arm measured 12X6 cm (Figure 1). No mucous membrane involvement was noted. Biopsies of skin specimens were obtained from both lesions for histologic diagnosis, which confirmed the presence of BCC (Figure 2). Because of the lesions' proximity to bone, bone radiographs were performed on the patient's chest, bilateral shoulders, and right arm, revealing punched-out lytic bone lesions in the ribs, left clavicle, scapulae, and right humerus (Figure 3A). Next, a bone scintigraphy scan was performed to survey the extent of disease, revealing a "superscan," with increased bony uptake in most of the axial skeleton above the pelvis along with other discrete areas of increased uptake in the upper extremities (Figure 3B). Additional laboratory data were not available. The patient was admitted to the medical center for improvement of his nutritional status and for the management of his skin lesions. On the seventh day of hospitalization, the patient unexpectedly died, and his family refused an autopsy.

Please refer to the PDF to view the figures

Comment

The first case of BCC metastatic to a submandibular lymph node was reported by Beadles⁸ in 1894. Few cases have been described in the literature since then, and rates of metastasis have been reported to be from 0.0028% to 0.4%, depending on the study protocol used.⁹ Although histologic confirmation of bone involvement is lacking, in the absence of other detectable malignancies, our objective clinical and radiographic findings point toward bone metastasis in our patient. A review of several case reports of BCC metastatic to bone demonstrates clinical and radiographic similarities with those of our patient (Table).

Please refer to the PDF to view the table

In contrast to nonmetastatic BCC, the age of onset of metastatic lesions is approximately 45 to 59 years, with an interval of approximately 9 to 11 years between primary tumor onset and spread.¹ However, cases of metastasis have been reported after latency periods of up to 23,²⁰ 26,²¹ and even 45³ years following diagnosis of primary lesions. Men are more often affected, and tumors generally are large, long-standing, and refractory to treatment.³ No significantly different histologic characteristics in metastatic tumors were identified by Wermuth and Fajardo²²; however, other authors have concluded that metatypical BCC, or BCC with foci of squamous differentiation, demonstrates more aggressive behavior and increased potential to metastasize.^9-11,16,19 Factors noted to be associated with an increased incidence of metastasis include long duration of a large primary lesion on the head or neck,²³ recalcitrance to treatment,¹ immunodeficiency combined with stromal independence of the tumor,²⁴ inadequate excision followed by immediate wound closure,²⁵ and lesion depth.²⁶ Farmer and Helwig¹⁶ noted a paucity of inflammatory cells in the vicinity of recurrent tumors, implicating the possibility of a defective cellular immune response as a contributing factor. Our patient's evolving history, however, was unclear due to his inability to provide an accurate account.

Total excision of primary tumors following recommended treatment guidelines does not tend to halt metastatic spread,⁴ and prior to discovery of metastases, lesions generally tend to recur locally following excision and/or radiation therapy.^1,4,9 Approximately equal rates of hematogenous and lymphatic spread are observed, and the lung is the most likely distant organ to be involved, followed by bone, liver, and pleura.³ Cases of bone metastasis may present with symptoms of spinal cord compression⁶ or anemia,¹⁵ as well as bone pain¹⁷ and pathologic fractures,^7,15 and tend to involve the lumbar spine more frequently than the thoracic and cervical regions.¹⁰ Our patient did not complain of any such symptoms indicative of osseous lesions, even with extensive bony involvement.

von Domarus and Stevens³ noted a slightly better survival rate among patients with lymphatic metastases versus those patients whose tumors disseminated hematogenously. Patients with metastatic BCC have a 5-year survival rate of approximately 10%; patients with distant spread typically survive only 10 to 14 months.¹ Prognosis is especially poor with metastases to the lungs, bone, or liver,^12,16 and palliative treatment generally is used in these cases.

Aggressive treatment should be pursued if BCC metastasis has been detected. Unfortunately, once distant metastasis occurs, cure is not possible and survival generally is short.¹² Excision of the primary lesion with free margins is the initial objective, but it may not always be possible due to the size or extent of the tumor. Therapeutic options for bone metastases include chemotherapy with agents such as cyclophosphamide, etoposide, fluorouracil, methotrexate, cisplatin, bleomycin, and doxorubicin.¹¹ Radiation therapy is an effective palliative treatment, but its use has not demonstrated increased survival benefit.¹² Laminectomy has been used for vertebral involvement.^10,12 Because of the rare nature of metastatic BCC, appropriate treatment protocols have not been formulated, and combination therapy with the above modalities generally is employed. Nevertheless, therapeutic response to treatment usually is poor. Because of our patient's untimely death, no treatment options were sought.