Introduction

Prostate cancer is a common malignancy in males worldwide. Acinar adenocarcinoma accounts for the majority of prostatic malignancies. Adenoid cystic carcinoma (ACC) of prostate is a rare entity constituting only about 0.01% of malignancies of prostate. ACC is usually found in major and minor salivary glands and infrequently in breast tissue. This tumor was first reported in salivary gland as a tumor with cribriform, glandular, and basaloid patterns containing mucous material. In prostate it arises from basal cell of prostatic ducts and acini. Only few case reports of ACC of prostate are available. We report a rare case of prostatic ACC in 49 year old male.

1 Case Report

A 49-year-old man came to the out-patient facility of Gujarat Cancer and Research Institute with complaints of urinary hesitancy, increase in frequency and nocturia since last 2 years with symptoms being aggravated since 3 months. There was no history of hematuria or any other significant previous medical history. His lab reports like hemogram and RFT were within normal range with Hb-12.3 g/dl, TLC-7700/cumm, Platelet count-441000/cumm, BUN-6 mg/dl and S.creatinine -0.67 mg/dl. Digital Rectal Examination (DRE) revealed a hard, palpable, non-tender and fixed nodular mass in prostate. Serum PSA level was within normal range (0.729 ng/mL). Due to a suspicious DRE, trans-rectal ultrasonography (TRUS)-guided routine, 12 core biopsies were taken from the prostate and sent for histopathological examination.

Histopathological examination revealed monomorphic tumor cells arranged in a cribriform pattern with intraluminal basophilic mucinous secretion (Figure 1). These tumor cells were small with scant cytoplasm and angulated hyperchromatic nuclei (Figure 2). Focally, the glands showed infiltration into the prostatic fibromuscular tissue (Figure 3). Perineural invasion was evident in the sections examined. Special stains like Periodic Acid Schiff (PAS) and Mucicarmine also stained mucin (Figure 4).

Figure 1 Scanner view showing tumor cells infiltrating normal prostate glands. Left: tumor Right: Normal prostatic glands

Figure 2 20x view showing cribriform pattern of the tumor cells

Figure 3 40x view showing small bland tumor cells with scant cytoplasm and dark compact anular nuclei surround pseudoglandular spaces with excess basement membrane and mucin

Figure 4 20x view sowing PAS positive excess basement membrane and mucin

Immunohistochemistry with monoclonal antibody for PSA was negative. c-kit showed strong cytoplasmic positivity (Figure 5). Ki-67 index showed 30% positivity. Diagnosis of ACC was made which was followed by radical prostatectomy. The patient was clinically stable during post-operative period. There was no progression of disease during the 2 months of follow-up.

2 Discussion

ACC is a rare subtype of prostatic malignancies. Very few cases have been reported in the literature. The largest case series includes 19 cases reported by Iczkowski et al. (2003).

ACC was first described in the salivary gland by bilroth in 1859. Other sites include maxillary antrum (Kim et al., 1999) and skin (Chang et al., 1999) where it has an aggressive biologic potential. However, histologically identical counterpart arises in lung (Kawashima et al., 1998) and breast (Arpino et al., 2002) and it has good prognosis. 

Histologically these cases exhibit either an adenoid or basaloid pattern. The basaloid pattern has an irregular solid clump, trabeculae and cellular masses composed of basaloid cells. The adenoid cystic pattern has a sieve like or cribriform arrangement of back to back infiltrating glands with central lumen containing mucin. Periodic Acid Schiff-Alcian blue (pH 2.5) stains mucin blue indicating acidic nature of the mucin. Perineural invasion is a common finding in these tumors. 

ACC of prostate is a tumor with a significant potential for recurrence, metastasis and extra prostatic extension, contrary to the conventional thought regarding this cancer (Iczkowski et al., 2003; Ahuja et al., 2011) making the accurate diagnosis of this entity essential. These cases are frequently underdiagnosed due to normal PSA (Prostate Specific Antigen) levels and negativity for PSA on immunostaining.

On IHC (Immunohistochemistry) the tumor cells show immunoreactivity for HMWCK (34βE12) in all reported cases (Kawashima et al., 1998; Kim et al., 1999; Chang et al., 1999; Iczkowski et al., 2003; Ahuja et al., 2011; Chang et al., 2013). Hence basal cells were thought to be the cells of origin. cKit is a promising marker which helps distinguish ACC at various sites from other benign and malignant tumors. It has a sensitivity of 82-88% and specificity of 87-88% for diagnosing ACC (Mino et al., 2003) A higher Ki67 index is used to distinguish ACC from basal cell hyperplasia of prostate. PSA shows negativity on IHC. Expression of Her2neu in ACC of salivary gland has been reported, but its credibility and usage in ACC prostate is limited. Smooth Muscle Actin (SMA) is shown to have positivity in 25% cases (Iczkowski et al., 2003), which suggests that some ACC may show a myoepithelial phenotype. CK7 positivity is restricted to the luminal cells only (Iczkowski et al., 2003).

The differential diagnosis for this rare tumor includes benign prostatic hyperplasia, poorly differentiated adenocarcinoma and poorly differentiated squamous cell carcinoma.

(1) An elevated Ki67 labelling index (>25%) helps to differentiate benign prostatic hyperplasia from ACC.

(2) Poorly differentiated adenocarcinoma is a close differential for ACC. Morphologically, abundance of extracellular PAS positive mucin favors ACC while acinar adenocarcinoma usually lacks a myxoid response. On IHC, cells of acinar adenocarcinoma are positive for PSA. Immunoreactivity for CK14 and immunonegativity for HMWCK favors adenocarcinoma while Negativity for PSA, CK14 and positivity for HMWCK favors ACC.

(3) Epithelial keratinization, intercellular bridges and lack of acinar pattern favors poorly differentiated squamous cell carcinoma. p63 immunoreactivity also helps to distinguish poorly differentiated squamous from ACC. 

There is no common consensus on the treatment for prostatic ACC. The commonly accepted effective treatment is Radical Retropubic Prostatectomy. The efficacy of hormonal therapy in treating ACC prostate is still controversial. But Shrawan et al (2014) reported hormonal therapy as a viable treatment option in patients with locally advanced and metastatic disease. Due to scarcity of cases prognosis is not well defined. A 5-year metastatic potential ranges from 5–10% in T1/T2 tumor to 50–85% in stage T3/T4 tumor (Chang et al., 2013).