Adenoid Cystic/Basal Cell Carcinoma of the Prostate: Review and Update

Prostate cancer is a common cause of mortality and morbidity worldwide; it is the most commonly diagnosed malignancy in men and the second leading cause of cancer death in Western countries. In the past 2 decades, the incidence of prostate cancer has increased worldwide, with a particular steep increase in the United States, partly because of serum prostate-specific antigen (PSA) screening.1 

Conventional acinar adenocarcinomas represent the large majority (>90%) of the tumors. Variants of conventional prostatic adenocarcinomas have been described and are important to recognize because the prognosis of these tumors may vary according to the type. These special variants have a wide histologic spectrum and originate from the 4 types of prostatic epithelium (Table). They can occur in a pure form or in association with classic/conventional adenocarcinomas.2 

A variant called adenoid cystic carcinoma in the prostate is now regarded as part of the morphologic continuum of basal cell carcinoma3; hence, we use the term adenoid cystic/ basal cell carcinoma. Adenoid cystic carcinoma was first reported in the salivary gland by Billroth4 in 1859; he described a tumor with cribriform, glandular, and basaloid patterns containing mucous material. Since this first report, these tumors have been described in the maxillary antrum,5 skin,6 lung,7 breast,8 cervix,9 and prostate.10 

Currently, in contrast to classic adenocarcinoma, the theory is that adenoid cystic/basal cell carcinoma of prostate is derived from basal cells rather than from epithelial cells of the ducts and acini. Basal cells are the stem cells compartment of the epithelium, with potential to differentiate along several different pathways, giving rise to various proliferating lesions including basal cell hyperplasia and basal cell carcinoma (which also includes adenoid cystic/basal cell carcinoma).11 

We describe here the clinical features, morphologic spectrum, and immunohistochemical findings for this unusual type of prostate carcinoma.

The age of patients with adenoid cystic/basal cell carcinoma of the prostate ranges from young to older individuals (28–78 years; mean, 50 years) with variable symptoms including nocturia, urgency, or progressive/acute urinary retention.12 Enlarged and partly indurated prostate gland on rectal examination is an important finding toward a clinical diagnosis.13 

The serum PSA is usually normal14,15 or slightly elevated when this carcinoma is present,12,16 and transurethral resection of prostate is the most common source of tissue for diagnosis.12,13 No preoperative imaging technique has provided findings sufficiently specific to detect this type of prostate tumor,16 which may be an incidental finding in a prostatectomy performed for conventional carcinoma.12 Although most reported adenoid cystic/basal cell carcinomas are of indolent behavior,2,17 the outcome for patients with adenoid cystic/basal cell carcinoma is currently uncertain as fewer tumors with local recurrence and metastases have been reported.12,15,18,19 Of interest is the fact that metastases involve liver, lung, and bowel but not bone, as is commonly observed in conventional prostate acinar adenocarcinomas.12 Because metastasis has been documented in 4 of 15 patients whose outcome is known in one series,12 the recommended treatment is similar to that of conventional adenocarcinoma, consisting primarily of surgical resection with periodic long-term follow-up. Radiation and chemotherapy may be helpful, but the results are inconsistent.15,20 

Grossly, tumors are white and fleshy, sometimes with microcysts, unlike acinar carcinoma, which is usually yellow.12 These tumors usually show ill-defined, infiltrative edges and involve the transition and peripheral zones.20 

Microscopically, adenoid cystic/basal cell carcinomas of the prostate can have either a predominant basaloid pattern like that of basal cell carcinoma of skin, or a cystically dilated acini and cells arranged in cribriform spaces surrounding eosinophilic-hyaline basement membrane–like material or basophilic mucinous secretion (Figure 1). Occasional glandular, trabecular, and solids areas can be found. The nuclei have basal cell features with angulated nuclear contours, and may be hyperchromatic or microvacuolated. In some cases, a sebaceous and squamous differentiation can be seen. Extensive perineural invasion and extraprostatic extension have been described (Figure 2).21 Mitoses are absent or only sparsely present. The stroma may show a desmoplastic or myxoid alteration.3 Given that the pattern of adenoid cystic carcinoma cannot be classified under the Gleason scheme and the pattern is not known with outcome, Gleason grading of these tumors is not currently recommended.

By immunohistochemical evaluation, adenoid cystic/ basal cell carcinomas of the prostate are usually positive for high-molecular-weight keratin (clone 34βE12) and cytokeratin 14, at least focally in all cases reported (Figures 3 and 4).12,20,22 The positivity of the tumor cells for this type of keratin is in keeping with the current hypothesis for the basal cell origin of this neoplasia as these antibodies have been considered specific markers for basal cell.11 

Staining for cytokeratin 7 tends to mark an adluminal cell population and basal cell cytokeratin (34βE12) stains the more peripheral cells.12 Staining for cytokeratin 20, p63, and S100 protein has been described in adenoid cystic/basal cell carcinoma of the prostate but the results are inconsistent.12,20 

Scattered chromogranin-positive cells have been reported in these tumors, and the tumor cells are consistently negative for synaptophysin.21,23,24 Elevated Bcl-2 protein and Ki-67 index can help establish the diagnosis of malignancy in prostate basal cell lesions.19,24,25 

Staining for PSA is usually negative,23,24,26 but in some cases positivity with this marker has been reported, especially in cases in association with concomitant acinar adenocarcinoma or inflammation.12,13,15 Additionally, tumor cells have been reported as negative for calponin, smooth muscle myosin heavy chain, and usually for smooth muscle actin.20,24,25 

Very few studies address the genetic alterations encountered in this group of tumors. Although loss of chromosomes 8p and 12p has been reported in conventional acinar adenocarcinoma,27,28 a normal karyotype has been found in basal cell tumors using comparative genomics hybridization.22 

The main differential diagnoses of adenoid cystic/basal cell carcinoma of the prostate include benign basal cell hyperplasia and cribriform pattern of acinar adenocarcinoma. Benign basal cell hyperplasia is a lesion that typically occurs in the prostate transition zone in elderly men and is frequently associated with benign nodular hyperplasia. The luminal spaces are bounded by secretory cells; the cribriform architecture does not form large confluent, expansive glandular patterns. Histologic features of malignancy-like necrosis, perineural invasion, and extraprostatic extension are not present. By immunohistochemical evaluation, benign basal cell hyperplasia and adenoid cystic/basal cell carcinoma share similar patterns of reactivity, expressing high-molecular-weight cytokeratin and cytokeratin 14 and variable positivity for PSA and prostate-specific acid phosphatase.13 

The cribriform pattern of acinar adenocarcinoma is characterized by small and large glands with bridges and the formation of lumens infiltrating the stroma. Necrosis can be seen in the lumen but not in eosinophilic amorphous material. Immunohistochemical evaluation shows that positive staining for PSA and prostate-specific acid phosphatase and negative staining for high-molecular-weight cytokeratin and cytokeratin 14 is typical of conventional acinar adenocarcinoma with cribriform features. Recently, positivity for p63 and c-Kit have been proposed as positive markers for adenoid cystic carcinomas of the salivary gland, but this staining pattern is not well documented in prostate tumors.29,30 

In addition, the possibility of a metastatic cloacogenic carcinoma of the anus and adenoid cystic/basal cell carcinoma arising in Cowper glands should be also addressed. The clinical features, including the epicenter of the main mass, are crucial for a correct diagnosis.10 

Adenoid cystic/basal cell carcinoma is a relatively rare but distinctive tumor in the prostate gland.1 Infiltrating basaloid cells forming dilated acinar and cribriform spaces with luminal basementlike material are characteristic for this tumor. Aggressive findings such as perineural invasion and extraprostatic extension may be found. Immunohistochemical evaluation shows that the tumor cells are at least focally positive for high-molecular-weight cytokeratin and cytokeratin 14. Staining for PSA is usually negative, but positivity has been reported. The main differential diagnosis includes benign basal cell hyperplasia and conventional adenocarcinoma with cribriform spaces. Clinically, the only difference from conventional adenocarcinoma is that the PSA is usually normal or only slightly elevated. These tumors have a biological potential that allows metastasis in a few cases; the current treatment consists primarily of surgical resection. Close, long-term follow-up is recommended.