BSCC has been defined in the 2005 WHO blue book as an aggressive high grade variant of squamous cell carcinoma composed of both basaloid and squamous components [
19]. The histogenesis of this neoplasm is controversial. Its first description [
1] and the current WHO classification on the Tumours of the Head and Neck [
19] suggest the tumour originates from totipotential cells in the basal layer of squamous epithelia.
A review of the literature shows that BSCC appears in both sexes but predominates in males between 60 and 80 years old [
19]. Alcohol and tobacco consumption are frequent antecedents. Clinical signs and symptoms are not specific and related to tumour location. The most frequent site is the piriform sinus and supraglottis and our experience agrees with this assertion. The possible relationship of BSCC and viruses is a matter of debate and has been reported in some locations, like nasopharynx [
10] and penis [
16]. The obtained data are however controversial; while Kleist et al. [
20] and El-Mofty et al. [
21] have very recently detected a higher frequency of HPV and HSV in basaloid tumours than in conventional squamous cell carcinomas in the head and neck, others [
22] have not found any difference.
Grossly, most of the previously reported BSCCs are flat or slightly elevated tumours, often with a central ulceration [
1,
4,
23], and our practice confirms it. Very few cases may show a polypoid pattern. Interestingly, these cases are always associated with a spindle cell component as the third constituent of the tumour [
24–
26].
It is well known that solid nests with the typical cell population, basaloid at the periphery and squamous at the centre, are the most common growth pattern of BSCCs. This arrangement is distinctive and specific of this tumour and can be recognizable even on fine needle aspiration cytology samples [
27]. However, histology relies as the only reliable diagnostic method [
1]. A wide range of different additional patterns have been described in BSCC, some of them quite unusual; for example, rosettes [
9], cystic spaces, true ductules [
1], spherules made of basal membrane material, and PAS+ crystalloids [
28]. As previously mentioned, a spindle cell component with epithelial immunophenotype quite infrequently takes part of the tumour [
24–
26].
By immunohistochemistry, BSCC expresses cytokeratins and EMA. Some authors [
19] recommend coktails of keratins composed of Cam 5.2, pankeratin AE/AE3 and CK7, while others [
1,
2,
29] propose the high molecular weight keratin 34βE12 as the most useful marker for this tumour. A “dot-like” pattern with vimentin has been also recorded in these tumours [
19]. Most cases are negative with neuroendocrine markers and with S-100 protein [
30,
31]. There is no specific immunohistochemical pattern to distinguish this tumour from others and its diagnosis is based on H&E sections. Quite recently, however, Coletta et al. [
32] have demonstrated the importance of cytokeratins 1, 7 and 14 in the diagnosis of BSCC and Emanuel et al. [
33] have stressed the value of p63 in making a distinction between BSCC and adenoid cystic carcinoma of the head and neck. These authors [
33] show that p63 positivity is diffuse in BSCC and partial in adenoid cystic carcinoma. Immunohistochemistry may be crucial in the recognition and diagnosis of endoscopic biopsies of BSCCs because these biopsies may be superficial or may not sample both basaloid and squamous components of the tumour. In this particular setting, the diagnosis of BSCC is hazardous.
The major histological component of BSCCs is basaloid, so its most important differential diagnosis is the solid variant of adenoid cystic carcinoma [
19], another quite infrequent neoplasm. As a matter of fact, adenoid cystic carcinoma does not show any tendency towards squamous differentiation, does contain myoepithelial cells and is essentially devoid of pleomorphic atypical cells, mitosis, and comedonecrosis [
23]. Small cell neuroendocrine carcinoma may share some morphological features, mainly in small endoscopic biopsies, but neuroendocrine markers and the “dot-like” immunostaining with keratins identifies it with reliability under the microscope. Some BSCCs contain cysts or pseudoadenoid structures and may mimic adenosquamous carcinoma, another rare entity in the area. The recognition of mucin positivity and true ductulo-acinar differentiation in adenosquamous carcinoma should resolve the dilemma.
The supposed higher clinical aggressiveness of BSCC compared with the conventional squamous cell carcinoma remains a continuous matter of debate. Banks et al. [
2], Luna et al. [
4], and De Sampaio et al. [
34] did not find significant differences in behaviour between these two neoplasms in different anatomical sites, while others [
35] did.
Winzenburg et al. [
35] were the first authors to correlate some histological variables of BSCC and prognosis. They found that cases with pure basaloid histology and comedonecrosis showed distant metastases in 46% of the patients and, consequently, fared worse. A predominantly basaloid histology was associated with distant metastases in 52% of their patients. Something similar happened with cases showing prominent stromal hyalinization, with 53% of patients displaying distant metastases. As many as 76% of their cases were in Stages III or IV at diagnosis, while only approximately 50% of our patients did. Surprisingly, their patients with vascular-lymphatic and/or perineural invasion did not present with distant metastases and survival was 100% [
35]. However, we have found vascular-lymphatic invasion is an ominous finding, with lymph node metastases and tumour-related death in all of our cases.
Node metastases are a quite common event in laryngeal, hypopharyngeal and tracheal BSCCs since they appear in regional and distant nodes in 75% and in 35–50% of the cases, respectively [
19]. As reflected since the first series [
1,
2,
4], lymph node status is a key factor in survival. Winzenburg et al. [
35] showed significant differences in survival of BSCC with and without lymph node metastases, with survivals of 18.6 and 47.6 months respectively, and our experience confirms it. Distant metastases do also occur in BSCCs with wide numbers ranging from 10% [
4,
36] to around 50% [
1,
2,
37] or even to 75% [
38]. We found them in 15% of our patients. Lung is the main target for distant metastases in BSCC. Sometimes the clinical status at diagnosis and the evolution of BSCCs seem to be especially aggressive.
Some authors have recently reported the value of p53, Ki-67 and e-cadherin [
39], p27
Kip1 [
40], and apoptosis inhibitor protein [
41] as independent predictors of prognosis in BSCCs, but these findings need further confirmation in large series and its acceptance and use in daily practice.
Finding a second primary tumour is a common clinical situation in the head and neck and was very soon recognized in BSCC. In fact, McKay and Bilous reported in 1989 [
42] a case BSCC in the hypopharynx who showed, in the surgical specimen, a microinvasive squamous cell carcinoma in the left arytenoid region. This possibility was fully recognized by 1991, when Seidman et al. [
43] presented a series of 11 BSCCs two of which, with tumours arising in the piriform sinus and vallecula, had synchronic squamous cell carcinomas in the oesophagus and palate, respectively. Associations with tumours outside upper aerodigestive tract have been reported by Banks et al. [
2] and Lam et al. [
44] in their series of esophageal BSCCs. We have observed it in 17.5% of our patients and support the Thompson’s advice [
23] for keeping in mind the possibility of finding a second primary tumour in any site, either synchronic or metachronic, when diagnosing a BSCC in the head and neck.
1 Ayman Gaafar,1 Maddi Garmendia,1 Carmen Etxezarraga,1 Francisco J. Bilbao,1 and José I. López2
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