Discussion
The age of patients with BCC of the prostate ranges from young to older individuals (28 to78 years; mean, 50 years) with variable symptoms including nocturia, urgency, or acute urinary retention [
3]. The enlarged and partly indurated prostate gland on rectal examination is an important finding toward a clinical diagnosis [
4].
Although prostate adenocarcinoma is always monitored by elevated PSA level, the serum PSA of BCC is usually within the normal range. Almost all the prostatic BCC with preoperative elevated PSA are diagnosed with concurrent prostate adenocarcinoma (Table
2). This may be explained by its assumed histological origin: the basal cells, which have no secretory function [
5]. Lacking typical clinical manifestations, the diagnosis relied on the pathological findings and the immunohistochemistry results.
Table 2
Serum prostate-specific antigen (PSA) level in prostate basal cell carcinoma(BCC)
| 15 | BCC | 1 (6.7%) |
4 | BCC+acinar carcinoma | 4 (100%) |
| 28 | BCC | 0 (0%) |
4 | BCC+acinar carcinoma | 1 (25%) |
Our cases | 3 | BCC | 0 (0%) |
According to the different pathological morphology, BCC can be histologically divided into adenoid-cystic and basaloid variants. Basaloid pattern is always infiltrated by irregular solid clumps, trabeculae and larger cellular masses composed of basaloid cells [
6]. The cells have uniform large pleomorphic nuclei and scant cytoplasm. While there is peripheral palisading and forming of solid nests, cribriforming is absent or minimal. The adenoid-cystic type is characterized by cylinders of hyalinized or mucinous stroma surrounded by nests of small epithelial cells, which give the tissue a perforated, sieve-like or cribriform appearance [
4]. All of our cases turned out to be the basaloid type. On immunohistochemistry, BCC tumor cells usually show a variable degree of positive immunostaining for p63 and high-molecular-weight cytokeratin 34bE12, both of which are suggestive of BCC. Conventional adenocarcinoma of the prostate is negative for these antibodies [
7].
For this rare malignancy, the differential diagnosis is indispensable, including benign basal cell hyperplasia (BCH), poorly differentiated adenocarcinoma and poorly differentiated squamous carcinoma. The differences between benign hyperplasia and the malignant can be drawn from the invasive growth pattern, extensive infiltration, perineural invasion, EPE, and the presence of necrosis. An elevated Ki67 labeling index can also allow distinction between benign and malignant prostatic basal cell lesions. Poorly differentiated adenocarcinoma may be nonreactive for PSA, which turned out to be hard to differentiate, but the presence of immunoreactivity for cytokeratin 14 and negative staining for high-molecular-weight cytokeratin were helpful in distinguishing it from BCC. Though primary squamous carcinoma may also originate from prostatic urethral epithelial cells, transitional epithelial cells around the urethra, basal cells of the prostatic acini or pluripotent stem cells from the prostate so that some immunohistochemistry marks may be the same as BCC, it has its own characteristics, including epithelial keratinization, obvious intercellular bridges, and lack of acinar structures. These characteristics can be helpful in distinguishing it from BCC.
BCC outcome is currently considered uncertain. McKenney
et al. suggested that many of the reported BCCs have been diagnosed with no definitive histological evidence of malignancy or aggressive clinical course [
8]. Grignon also admitted these lesions as a neoplasm of low malignant potential [
9]. However, our presented cases showed malignant behavior with EPE and distant metastasis were found just six months after the regional treatment on average. According to the literature, relatively high Ki67 staining may suggest aggressive behavior. Bohn reported that Ki67 is a useful marker determining proliferation; the proliferative rate of BCH and florid BCH is usually lower than BCC [
10]. Among Ali’s reported 29 cases [
1], seven of the cases presented Ki67 staining over 25%, and three (42.85%) of them were found with distant metastasis in the follow-up. While there were only four cases (13.79%) found with distant metastasis in all. Combined with our cases, which all presented Ki67>25%, we are inclined to draw the conclusion that relatively high Ki67 staining was related to the distant metastasis. However, more cases are needed to analyze whether there is a correlation between high Ki67 staining and BCC distant metastasis. Therefore, it alarms us that aggressive treatment is required as soon as the diagnosis of BCC is established.
There is no consensus on treatment for prostatic BCC. The commonly accepted effective treatment is radical retropubic prostatectomy (RRP) [
5]. Though there are few reported treating experiences about RRP, it was helpful in shrinking the size of the primary tumor volume in our two cases. But its effect on preventing the tumor cells from metastasis may be limited, as distant metastases were found in the following few months.
It is still controversial whether hormonal therapy is effective in treating prostatic BCC. Koochekpour reported that androgen suppression therapy is the gold standard, first-line therapy for advanced/metastatic disease [
11]. However, Segawa reported that their patient attempted androgendeprivation therapy, but without success [
12]. All of our three cases also received hormonal therapy but no evidence was found that it was helpful with their prostatic BCC. Combined with BCC’s origin, which is stated above, we are inclined to conclude that hormonal therapy has no effect on prostatic BCC. Further study with a larger cohort is needed in the future.
Though distant metastases were found just a few months after the initial treatment, the first patient still lives with a relatively high quality of life after distant metastases were recorded two years ago. So positive treatment according to our treating experience is strongly recommended. Chemotherapy may be helpful but the results are not consistent [
13].
An exact prognosis of prostatic BCC is not known due to the scarcity of reported cases. Iczkowski
et al. reported that a five-year metastatic potential ranges from 5 to 10% in T1/T2 tumor to 50 to85% in stage T3/T4 tumor [
14]. This conclusion is partially confirmed by our cases, all of them can be diagnosed as T4 stage and distant metastases were detected within five years after diagnosis.
Competing interests
The authors declare that they have no competing interests.
Authors’ contributions
KC and BD conceived of the concept, participated in drafting the manuscriptand conducted the critical review. YYQ collected patients’ partial clinical data and revised the manuscript. YYK and JNW reviewed the pathological slides and revised the manuscript. DWY supervised the project and revised the manuscript. XDY, SLZ, HLZ, YZ and WQY took part in the treatment of the patients, assembled data, and followed up with patients. All the authors read and approved the final version and agreed to publish the manuscript.