March 2006

Fig3.

Fig.4

Fig.5

Fig.6

Diagnosis: Basal cell carcinomas, metastatic.

Histopathology: A wedge biopsy was performed for the lesion on the right arm. A punch biopsy was performed for the lesion on the back. Microscopic features of the right arm wedge biopsy were consistent with basal cell carcinoma, infiltrative to subcutis (Figures 3,4). Microscopic features of the biopsy of the back lesion was also consistent with basal cell carcinoma.

Clinical Course: To further evaluate metastatic spread, computed tomographic examination was performed of the chest, abdomen, and pelvis with intravenous contrast. Examination of the chest revealed multiple bilateral pulmonary nodules as large as 2 x 1.2 cm, most consistent with metastatic disease (Figures 6). There was a 2.4 x 2.3 cm soft tissue mass in the right axilla, as well as enlarged right subclavicular lymph nodes. The right humerus demonstrated defects consistent with osteomyelitis. Examination of the abdomen and pelvis revealed multiple enhancing lesions throughout the liver as large as 7.4 x 5.3 cm, most consistent with metastatic disease (Figures 7).
In addition to the Dermatology service, General Surgery, Medical Oncology, and Radiation Oncology all evaluated the patient. The patient declined amputation, radiation therapy, and chemotherapy. For her iron deficiency anemia, she received a total of 6 units of packed red blood cells, which increased her hematocrit to 32, and was started on ferrous sulfate. In terms of the question of osteomyelitis, she remained afebrile with normal white blood cell count, without discharge from her wound. She was treated with Unasyn intravenously and transitioned to augmentin. The patient was discharged after arranging for home health nursing assistance.

Discussion: Basal cell carcinomas (BCC) rarely metastasize with fewer than 250 reported cases and an estimated rate of metastasis of 0.003% to 0.5%.1 Criteria to diagnose metastatic BCC include: primary cutaneous not mucosal BCC, metastatic site distant from primary site (excluding direct extension), and comparable histopathologic features of primary and metastatic BCC (1, 2)
The low metastatic rate of BCC has been explained by the tumor's stromal dependency (3 ). Risk of BCC metastasis has been linked to tumor size, depth of local invasion, ulceration(4,5), perineural spread,(6) blood vessel invasion,6 and local tumor recurrence (7, 8). Basosquamous subtype may also increase metastatic potential(9) Metastases may be more common in males (2:1 in one review (6 ). Immunosuppression does not seem to impact metastatic potential (6 ) In one review, the time between appearance of the primary BCC and metastasis was 9 years.6 After metastasizing, BCC tends to behave more aggressively with up to 50% mortality by 8 months after metastases become symptomatic.6 BCC of the scalp and genitalia may have higher rates of metastasis.10 Lymph nodes, bone, and lung are the most frequent sites of metastases (6, 11, 12).
Because of the rarity of metastatic BCC, response to therapy remains poorly defined. For localized metastases, excision is commonly possible (7, 13 ) For distant metastases, surgery, radiation therapy (14) and/or chemotherapy15 may be used. Cis-platinum may be more effective than other forms of chemotherapy (15).

References:
1. Robinson JK, Dahiya M. Basal cell carcinoma with pulmonary and lymph node metastasis causing death. Arch Dermatol. May 2003;139(5):643-648.
2. Lattes R, Kessler RW. Metastasizing basal-cell epithelioma of the skin; report of two cases. Cancer. Jul 1951;4(4):866-878.
3. Pinkus H. Epithelial and Fibroepithelial Tumors. Arch Dermatol. Jan 1965;91:24-37.
4. Randle HW. Basal cell carcinoma. Identification and treatment of the high-risk patient. Dermatol Surg. Mar 1996;22(3):255-261.
5. Lo JS, Snow SN, Reizner GT, Mohs FE, Larson PO, Hruza GJ. Metastatic basal cell carcinoma: report of twelve cases with a review of the literature. J Am Acad Dermatol. May 1991;24(5 Pt 1):715-719.
6. von Domarus H, Stevens PJ. Metastatic basal cell carcinoma. Report of five cases and review of 170 cases in the literature. J Am Acad Dermatol. Jun 1984;10(6):1043-1060.
7. Berlin JM, Warner MR, Bailin PL. Metastatic basal cell carcinoma presenting as unilateral axillary lymphadenopathy: report of a case and review of the literature. Dermatol Surg. Nov 2002;28(11):1082-1084.
8. Siegle RJ, Wood T. Nonrecurrent primary basal cell carcinoma of the lower extremity with late metastasis. J Dermatol Surg Oncol. Jul 1994;20(7):490-493.
9. Farmer ER, Helwig EB. Metastatic basal cell carcinoma: a clinicopathologic study of seventeen cases. Cancer. Aug 15 1980;46(4):748-757.
10. Snow SN, Sahl W, Lo JS, et al. Metastatic basal cell carcinoma. Report of five cases. Cancer. Jan 15 1994;73(2):328-335.
11. Mikhail GR, Nims LP, Kelly AP, Jr., Ditmars DM, Jr., Eyler WR. Metastatic basal cell carcinoma: review, pathogenesis, and report of two cases. Arch Dermatol. Sep 1977;113(9):1261-1269.
12. Safai B, Good RA. Basal cell carcinoma with metastasis. Review of literature. Arch Pathol Lab Med. Jun 1977;101(6):327-331.
13. Christian MM, Murphy CM, Wagner RF, Jr. Metastatic basal cell carcinoma presenting as unilateral lymphedema. Dermatol Surg. Oct 1998;24(10):1151-1153.
14. Christie DR. The benefit of postoperative radiotherapy in metastatic basal cell carcinoma. Aust N Z J Surg. Jul 1997;67(7):491-493.
15. Pfeiffer P, Hansen O, Rose C. Systemic cytotoxic therapy of basal cell carcinoma. A review of the literature. Eur J Cancer. Jan 1990;26(1):73-77.

This case is presented by Drs. David Berk and Margaret Mann.