Why Does Basal Cell Carcinoma Metastasize So Rarely?

Abstract

Malignant lumors are characterized by their ability to invade adjacent tissues and to metastasize. A few tumor types show invasive behaviour and usually fail to metastasize during their entire life histories; examples are chordoma, craniopharyngioma, glioma and basal cell carcinoma. Of these, basal cell carcinoma is by far the commonest, and the rare event of its metastasis has been recorded to date in almost 100 cases. It is important to consider whether analysis of these cases can provide any broad clues as to how this invasive tumor has, on occasion, gained metastatic potential. In recent years many studies on tumor cell mobility, enzyme production and cell surface characteristics^-^ have revealed the complexity of the metastatic process but so far no clear pattern has emerged from the detail. It is not the intention here to add to detailed knowledge of the metastatic process, nor to contribute new experimental data, rather to take a broad viewpoint in the hope of identifying a direction or area in which this basic research might profitably be applied. Metastasis of Basal Cell CarcinomaReview of 38 cases described in 24 papers^"^^ reveals the following information. The primary tumor is almost always situated on the face or scalp and the histological diagnosis is beyond reasonable doubt in all but a very few cases. In most accounts metastasis is not associated with any particular or unusual histological pattern of basal cell carcinoma, nor do the metastases differ his-tologically from the primary tumors. The primary tumor almost invariably extends over an unusually large area and deeply erodes underlying structures. There is a long clinical course including repeated recurrences and attempts at treatment, which has consisted of both surgery and radiotherapy. The age of the patient at onset of the tumor, when known, ranges from 17-68 years (mean 44 years). The interval between onset of the tumor and detection of metastasis ranges from 4-25 years (mean 11 years). The site of metastasis in most cases is local lymph nodes. Blood-borne spread is less common and tends to affect the lungs, liver and bone. Metastasis in the spleen, pancreas, dura mater, pericardium and kidney has also been recorded. Metastasis may be restricted to lymph nodes, lung, bone or liver, but multiple organs are often involved. (A capricious pattern of metastasis is also seen in other metastasizing tumors.) When blood-borne metastasis has occurred, the tumor behaves with a high degree of malignancy and prognosis is poor. DiscussionLarge tumor size is an outstanding feature of metastasizing basal cell carcinomas. This is consistent with the long period before metastasis and the multiple treatments and recurrences. The face is an area in which treatment might err on the conservative side; furthermore, the subcutaneous tissue here is thin and underlying muscle and bone are vulnerable to invasion.This relationship between tumor size and metastatic potential is seen in most tumors, giving rise to good prospects of cure if the tumor is excised before...

Metastatic basal cell carcinoma with loss of p63 and mismatch repair proteins

“…The tendency for BCC not to metastasize is hypothetically related to its dependence on the surrounding dermal stroma 6 . Metastases occur when either tumor cells lose this dependence or when tumor emboli are large enough to include attached stroma and are transported to distant sites via lymphatics or blood vessels 6 .…”

“…Metastases occur when either tumor cells lose this dependence or when tumor emboli are large enough to include attached stroma and are transported to distant sites via lymphatics or blood vessels 6 . In addition, unlike sebaceous carcinomas, most BCCs display strong expression of mismatch repair proteins, particularly in peripheral cells in tumor nests near the stromal interface, contributing to their normally indolent behavior 7 .…”

Metastatic Basal Cell Carcinoma Originating in the Supra‐Parotid Region

“…Questions of deficient host immunity have been raised but never specifically defined or proven . Blewitt conjectured that metastatic potential may be significantly related to the probability of tumor contacts with large‐caliber vessels . He postulated that only reasonably‐sized vascular lumina could transmit a tumor embolus large enough to accomodate a viable tumor‐stroma complex.…”

“…He postulated that only reasonably‐sized vascular lumina could transmit a tumor embolus large enough to accomodate a viable tumor‐stroma complex. Unlike other metastatic neoplasms, successful implantation of metastatic BCC may require stromal, as well as tumor, elements . Therefore the vascular density and lumen diameter in the tumor site may be important in dictating the likelihood of viable metastatic spread.…”

Metastatic Basal Cell Carcinoma in Acquired Immunodeficiency Syndrome—Related Complex

“…N Engl J Med 1981;305:1425-1431. 16. Hsu SM, Raine L, Fanger H: A comparative study of the peroxidase-antiperoxidase method and an avidin-biotin complex method for studying polypeptide hormones with radioimmunoassay antibodies.…”