Basal cell carcinoma (BCC) is the most common type of human cancer, often l
ocally invasive, and following a benign clinical course. However, a proport
ion of BCCs do recur after treatment, causing extensive local tissue destru
ction, seldom metastasizing. Morphological methods to unequivocally disting
uish the aggressive forms of these tumors (BCC2) from the ordinary ones (BC
C1) have so far been lacking. Apoptosis, or programmed cell death, is thoug
ht to be important for the death of tumor cells in various stages of carcin
ogenesis. We analyzed the extent of apoptosis in BCCs of head and neck in a
morphological, morphometric, and electron-microscopic study, to estabilish
on a retrospective basis, the relative frequency of recurrence of tumors s
howing different apoptotic rates. We found that BCC1 showed lower apoptotic
index (AI) than BCC2 [BCC1: AI from 2.03 to 10.45% (mean value: 5.98%) BCC
2: AI from 21.91 up to 43.82% (mean value: 39.82%)]. The morphometric analy
sis of both BCC1 and BCC2 revealed significant differences between the valu
es concerning nuclear area, length, perimeter, and roundness of the apoptot
ic cells with respect to the 'viable' neoplastic cells. Electron-microscopy
confirmed that the features of morphological apoptotic cells were characte
ristic of programmed cell death. We hypothesized that low apoptotic rates i
n BCC1 could be indicative of a good prognosis. In fact, this corresponded
to an 'expansive' but not still invasive neoplastic state. In this phase, h
owever, the tumor cells may constitute the target for genetic changes trigg
ered by enviromental physical or chemical mutagenic agents, such as UV rays
. BCC2, then, could be the result of newly selected mutated neoplastic cell
ular clones, with more aggressive biological behavior. The high apoptotic l
evel found in BCC2 could thus be used as an indirect alarm signal from path
ologists. This hypothesis seems to be supported by most of the current data
in the literature and by the clinical outcome of BCC2 of our series. In ou
r opinion, routine evaluation of apoptosis in BCCs could be proposed to fac
ilitate their sub-classification, contributing toward the evaluation of the
prospective outcome of the individual patients. (C) 1999 Elsevier Science
Ltd. All rights reserved.