Atypical presentation of metastatic basal cell carcinoma.

Abstract: Basal cell carcinoma is an indolent, slow-growing tumor that rarely metastasizes. Approximately 70% of tumors occur in the head and neck regions. If a basal cell tumor metastasizes, it usually spreads to the regional lymph nodes first, followed by the lungs. We describe a patient with basal cell carcinoma of the right lower extremity with skin metastases. Skin biopsy of one tumor revealed fibroepithelioma of Pinkus, a rare variant of basal cell carcinoma.

Key Words: basal cell carcinoma, fibroepithelioma of Pinkus, lower extremity, skin metastases

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Basal cell carcinoma is the most common skin malignancy in the white population, accounting for approximately 75% of all nonmelanoma skin cancers in the United States. (1) Arising in epidermis containing hair follicles, it follows an indolent course, with a rare ability to metastasize due to a dependence on growth factors derived from local stroma. (2,3) Indeed, the incidence of metastasis is approximately 0.1% in surgical centers; (4,5) more than 205 cases of metastatic basal cell carcinoma have been documented in the world literature. (1,5,6) Risk factors for metastatic basal cell carcinoma include age, immune status, size of primary tumor, and depth of invasion as well as environmental factors such as ultraviolet and ionizing radiation. (1,6-8)

We describe a rare case of metastatic basal cell carcinoma presenting on the right foot of a female patient with multiple cutaneous nodules along the right lower extremity to the gluteal region. A literature search has revealed limited information regarding metastatic basal cell carcinoma of the skin; moreover, few cases involve basal cell carcinoma of the lower extremities. (4,6-12) In addition, skin biopsy specimens from our patient revealed fibroepithelioma of Pinkus, a variant of basal cell carcinoma. (2)

Case Report

A 48-year-old, previously healthy, white woman noticed small, scaly lesions on her right instep approximately three years previously. Although pruritic, she remained unconcerned until they began to enlarge, bleed, and spread superiorly up the right leg. She denied a history of radiation treatments, immune disorders such as human immunodeficiency virus, local leg and/or foot trauma, or previous skin cancers. One brother had died as a result of melanoma at age 54.

Physical examination revealed a well-developed white woman in no acute distress. Skin evaluation revealed the presence of the primary tumor: a pinkish, fleshy nodule approximately 1.2 cm on the right medial forefoot. In addition, multiple papulonodular lesions ranging in size from pinpoint to 1 to 3 cm extended from the base of the first metatarsal to the right calf, along the popliteal fossa, up the medial thigh, and into the gluteal fold and intertriginous region of the right groin. No skin changes were noted on the soles of her feet. All lesions were pearlescent, firm, rubbery, nonbleeding, nonulcerated, and nontender; they followed a well-demarcated line approximately 3 cm wide. No extremity edema was present. In the right inguinal region, lymph nodes at the upper limits of normal size, 1 to 1.5 cm, were palpated. Physical examination was otherwise unremarkable (Figs. 1-5).

Computed tomographic scans of the chest, abdomen, and pelvis were negative for adenopathy or masses. A skin biopsy of a tumor from the right calf revealed basal cell carcinoma; a second biopsy of a lesion from the right lower extremity showed fibroepithelioma of Pinkus. Sentinel node biopsy of the right inguinal region was negative.

A radiation treatment plan was offered to the patient as the primary mode of therapy. Surgical removal of all skin lesions was not considered, because of the extensive nature of the dermal lymphatic spread.

Discussion

As outlined by Lattes and Kessler, (10) metastatic basal cell carcinoma is defined by the following criteria: 1) the primary tumor must occur in skin containing hair follicles and not the mucous membranes; 2) metastasis cannot be by simple extension, but occurring at a site distant from the primary tumor; 3) the primary tumor and the metastasis must have similar histologic appearances of basal cell carcinoma; and 4) squamous cell features must not be present in the lesions. Metastatic spread occurs mainly by either lymphatic or hematogenous routes, both at an equally frequent rate. (4) Subcutaneous spread is rare, the incidence reported at approximately 9.7% among cases of metastatic basal cell carcinomas. (6) Mikhail et al (7) reported a female patient with a 2.5-cm metastatic lesion excised from the SC layer of the thigh. Unlike our case study, however, the primary tumor was "extensive, ulcerated" and originated from the outer canthus of the right eye; moreover, the

patient had multiple bony metastasis. (7)

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In addition, basal cell carcinoma of the lower extremities is rare in the literature: Coletta et al (12) described a male patient with basal cell carcinoma presenting in the leg with regional lymph node and skin metastasis. Again, unlike our patient, the primary lesion was ulcerated and large, approximately 7.5 cm; furthermore, the metastatic skin lesions had "central vesicles" with dermal spread to the trunk, arms, neck, and head. The patient developed bony metastases and died within 2 years of presentation. Also, in contrast to our report, Costanza et al (13) described a "large, fungating" primary tumor of the left thigh in a male patient that had been growing for 10 years; the tumor invaded the soft tissues within the anterolateral compartment and then metastasized to the lungs. Siegle and Wood (11) documented a 78-year-old woman with a "deeply indurated mass" in the left inguinal region consistent with metastatic basal cell carcinoma after presenting with basal cell carcinoma of the tibia 11 years earlier. Many metastatic basal cell tumors present with primary tumors that are invasive and tissue-destructive. Indeed, large basal cell carcinomas associated with destructive tissue changes have an increased frequency of metastasis, representing approximately 75% of metastatic basal cell tumors. (6) Nevertheless, we report a case that is atypical, with lower extremity involvement and in-transit, dermal lymphatic metastasis; also, these tumors do not produce local tissue destruction or distant organ metastasis.

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Histologically, there is no "obvious" difference by light or electron microscopy between metastatic and nonmetastatic basal cell carcinoma. (14) However, the factors that determine whether basal cell carcinoma will metastasize have not been clearly elucidated. Dr. Herman Pinkus proposed that the low incidence of basal cell metastasis might be related to local stromal dependence. (2)

Conclusion

We describe a very unusual case study that challenges the traditional anatomic distribution of basal cell carcinoma and the type of metastatic spread. (1,4-7) We emphasize that physicians must be aware that basal cell carcinoma may atypically present as small, nonulcerated tumors in the lower extremities with dermal lymphatic metastases. Given the finding that the median survival after diagnosis is only 8 months, (4) we recommend prompt follow-up and treatment for survival benefit.

Accepted June 24, 2003.

Copyright [c] 2004 by The Southern Medical Association

0038-4348/04/9703-0305

References

1. Fathman EM, Geisel EB. Basal cell carcinoma, in Odom RB, James WD, Berger TG (eds): Andrews' Diseases of the Skin: Clinical Dermatology. Philadelphia, W.B. Saunders Co., 2000, ed 9, pp 820-829.

2. Pinkus H. Premalignant fibroepithelial tumors of skin. Arch Dermatol 1953;67:598-615.

3. Cooke D, Englis MR, Morriss JM. Basal cell carcinoma, in Fitzpatrick TB, Johnson RA, Wolff K, et al (eds): Color Atlas & Synopsis of Clinical Dermatology: Common & Serious Diseases. New York, McGraw-Hill, 2001, ed 4, pp 261-265.

4. 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 1984;10:1043-1060.

5. Cotran RS. Metastasizing basal cell carcinomas. Cancer 1961;14:1036-1040.

6. Snow SN, Sahl W, Lo JS, et al. Metastatic basal cell carcinoma: Report of five cases. Cancer 1994;73:328-335.

7. Mikhail GR, Nims LP, Kelly AP Jr, et al. Metastatic basal cell carcinoma: Review, pathogenesis, and report of two cases. Arch Dermatol 1977;113:1261-1269.

8. van der Riet P, Karp D, Farmer E, et al. Progression of basal cell carcinoma through loss of chromosome 9q and inactivation of a single p53 allele. Cancer Res 1994;54:25-27.

9. Roth MJ, Stern JB, Haupt HM, et al. Basal cell carcinoma of the sole. J Cutan Pathol 1995;22:349-353.

10. Lattes R, Kessler RW. Metastasizing basal-cell epithelioma of the skin. Cancer 1951;4:866-878.

11. Siegle RJ, Wood T. Nonrecurrent primary basal cell carcinoma of the lower extremity with late metastasis. J Dermatol Surg Oncol 1994;20:490-493.

12. Coletta DF, Haentze FE, Thomas CC. Metastasizing basal cell carcinoma of the skin with myelophthisic anemia. Cancer 1968;22:879-884.

13. Costanza ME, Dayal Y, Binder S, et al. Metastatic basal cell carcinoma: Review, report of a case, and chemotherapy. Cancer 1974;34:230-235.

14. Sarma DP. Metastatic basal cell carcinoma: Electron microscopic study of the primary and the metastatic lesion. South Med J 1980;73:799-801.

RELATED ARTICLE: Key Points

* Basal cell carcinoma is characterized by a slow, indolent course, with a rare ability to metastasize.

* Dr. Herman Pinkus first identified fibroepithelioma of Pinkus in 1953. It is a type of basal cell carcinoma with a histologic appearance of thin strands of basaloid cells anastomosing with fibrotic stroma.

* The median age of occurrence of metastatic basal cell carcinoma is 45 years, with a median survival after metastases of only 8 months.

* Metastasis most commonly occurs to the regional lymph nodes, lung, and bones.

* Limited information is available regarding basal cell carcinoma of the lower extremity with metastatic spread to the skin.

Kyle T. Colvett, MD, Floranne C. Wilson, MD, and Ryan A. Stanton, MD

From the Department of Radiation Oncology, Johnson City Medical Center, James H. Quillen College of Medicine, Johnson City, TN.

Reprint requests to Kyle T. Colvett, MD, 400 N. State of Franklin Road, Johnson City, TN 37604-6094. Email: [e-mail]