Introduction

Prostate cancer is one of the most common male cancers in the U.S. and European countries.¹ However, macroscopic cyst formation of prostatic adenocarcinoma is extremely rare. The diagnostic definition and prognosis remain unclear due to the rare incidence. A previous report indicated possible pathological features of ductal carcinoma.² Ductal carcinoma of the prostate may often be accompanied by gene mutations, including DNA repair mutations, which result in a poor prognosis.³ We report herein a case of macrocystic ductal adenocarcinoma of the prostate in an 82-year-old man that completely regressed after initiation of primary androgen deprivation therapy.

Clinical Case

An 82-year-old man was referred to Chiba university hospital due to elevated prostate specific antigen (PSA) of 5.48 ng/ml. He had a history of transverse colon cancer that was surgically removed 7 years ago without a sign of recurrence. Digital rectal examination showed a slightly hard nodule at the left lobe of the prostate. The patient presented with no evident urinary symptom with a total International Prostate Symptom Score of 4. The initial PSA was 6.53 ng/ml with a testosterone level of 378 ng/dl, together with luteinizing hormone/follicle-stimulating hormone of 1.99/5.00 mIU/ml. Magnetic resonance imaging (MRI) presented a multifocal cystic mass protruding ventrally from the prostatic transition zone. The cystic mass was 60 mm in length, and dorsally it is embedded in the peripheral zone and seminal vesicle. There was a high-signal structure inside the lesion on T1-weighted imaging, which appeared to be a hemorrhagic component. Caudally, there were multiple nodules with low signal on T2-weighted imaging and abnormal signal on diffusion-weighted imaging/apparent diffusion coefficient map (Fig. 1, A and B). Based on the findings, prostate cancer was suspected with Prostate Imaging Reporting and Data System^® score of 5 with seminal vesicle invasion. No distant metastatic lesion was identified on bone scan and computerized tomography. Based on the imaging, the clinical stage was determined as cT3bN0M0.

The pathological finding from the transrectal biopsy represented tall columnar atypical epithelium with pseudostratified nuclei and low papillary structures representing the ductal adenocarcinoma with the additional component of the acinar adenocarcinoma (Fig. 2, A and B). The tumor cells were immunoreactive for NKX3.1 and without surrounding p63 positive basal cells (Fig. 2, C and D). Based on the findings, the diagnosis of macrocystic ductal adenocarcinoma of prostate was made with a Gleason score of 4+4.

Figure 1. MRI imaging. Axial (A and C) and sagittal (B and D) T2-weighted MRI of the prostate. The macrocystic appearance before treatment (A and B) showed remarkable regression 9 months after androgen deprivation therapy (C and D).

Figure 2. Pathological findings. Hematoxylin and eosin staining of the ductal adenocarcinoma with objective magnification ×10 (A) and objective magnification ×20 (B) from the prostate biopsy sample showing mixed acinar and macrocystic ductal carcinoma of the prostate with Gleason score 4+4. Immunohistochemistry for p63 shows that the tumor is negative for basal cells (C). Positive NKX3.1 staining represented the prostatic origin of the tumor (D).

Figure 3. Post-treatment course of PSA. The initial PSA was 6.5 ng/ml. After initiation of ADT, the PSA level decreased gradually and reached a nadir of 0.01 ng/ml and stayed at the lowest level up to now.

Due to the advanced age, the patient received androgen deprivation therapy (ADT) with leuprorelin and bicalutamide. After 9 months of primary ADT, the PSA reached 0.01 ng/ml and currently continued at the lowest level (Fig. 3). The MRI image at this point represented complete regression of the cystic lesion (Fig. 1, C and D) without evidence of metastasis.

Discussion

Macrocystic ductal adenocarcinoma of prostate is extremely rare and has only been reported in case reports and case series.^2,4–6 A previous report described a median PSA of 35.22 ng/ml with urinary and/or intestinal obstructive symptoms. The size of the tumor ranges from 1.8 to 12 cm. About 75% of the cases represent ductal carcinoma.⁴ The current case was an 82-year-old man with an initial PSA of 6.5 ng/ml without urinary symptoms, which may represent a rather early diagnosis of macrocystic ductal adenocarcinoma of prostate. The differential diagnosis of macrocystic adenocarcinoma of the prostate may include liposarcoma, lymphangioma, leiomyoma with cystic degeneration, teratoma, multilocular peritoneal inclusion cyst and prostatic abscess. Furthermore, cystic lesions in the pelvis, such as müllerian cysts, utricle cysts and seminal vesicle cysts, may also be considered at diagnosis.⁷ An immunohistochemical approach such as NKX3.1, AMACR/p504S and PSA staining may provide the precise origin of the tumor.

Conclusion

Ductal carcinoma of the prostate is often related to poor outcome. Nearly 50% of cases contain DNA damage repair gene alteration, together with the 30% of PI3K and WNT pathway mutation.³ Thus, patients with ductal carcinoma of the prostate may be suitable to be offered next-generation sequencing to guide treatment, including immune checkpoint inhibitor and/or PARP inhibitor, or toward an appropriate clinical trial. On the other hand, some studies indicate a favorable clinical course, such as prostatic intraepithelial neoplasia-like ductal adenocarcinoma.⁸ In current practice, genetic testing may give us the clue to predict the prognosis as well as the way to construct the treatment strategy.