CASE REPORT: A Case of Macrocystic Ductal Adenocarcinoma of the Prostate
By: Shinichi Sakamoto, MD, PhD; Ayumi Fujimoto, MD, PhD; Masayuki Ota, MD, PhD; Yusuke Imamura, MD, PhD; Toyonori Tsuzuki, MD, PhD; Jun-ichiro Ikeda, MD, PhD; Tomohiko Ichikawa, MD, PhD | Posted on: 01 Jun 2022
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.
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.
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.
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.
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.
- Sung H, Ferlay J, Siegel RL et al: Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71: 209.
- Kojima F, Koike H, Matsuzaki I et al: Macrocystic ductal adenocarcinoma of prostate: a rare gross appearance of prostate cancer. Ann Diagn Pathol 2017; 27: 7.
- Schweizer MT, Antonarakis ES, Bismar TA et al: Genomic characterization of prostatic ductal adenocarcinoma identifies a high prevalence of DNA repair gene mutations. JCO Precis Oncol 2019; 3: PO.18.00327.
- Paner GP, Lopez-Beltran A, So JS et al: Spectrum of cystic epithelial tumors of the prostate: most cystadenocarcinomas are ductal type with intracystic papillary pattern. Am J Surg Pathol 2016; 40: 886.
- Giganti F, Allen C, Sridhar A et al: Mixed acinar and macrocystic ductal prostatic adenocarcinoma. Lancet Oncol 2021; 22: e37.
- Uguen A, Doucet L, Badic B et al: Cystic epithelial tumors of the prostate: one case supporting a continuous spectrum from cystadenoma to cystadenocarcinoma with ductal features. Am J Surg Pathol 2016; 40: 1719.
- Shebel HM, Farg HM, Kolokythas O et al: Cysts of the lower male genitourinary tract: embryologic and anatomic considerations and differential diagnosis. Radiographics 2013; 33: 1125.
- Tavora F and Epstein JI: High-grade prostatic intraepithelial neoplasialike ductal adenocarcinoma of the prostate: a clinicopathologic study of 28 cases. Am J Surg Pathol 2008 32: 1060.