Macrocystic ductal adenocarcinoma of prostate: A rare gross appearance of prostate cancer

    Macrocystic ductal adenocarcinoma of prostate: A rare gross appearance of prostate cancer Fumiyoshi Kojima, Hiroyuki Koike, Ibu Matsuzaki, Yoshifumi Iwahashi, Kenji Warigaya, Masakazu Fujimoto, Kazuo Ono, Youji Urata, Yasuo Kohjimoto, Isao Hara, Shin-ichi Murata PII: DOI: Reference:

S1092-9134(16)30280-5 doi:10.1016/j.anndiagpath.2016.12.002 YADPA 51136

To appear in:

Annals of Diagnostic Pathology

Please cite this article as: Kojima Fumiyoshi, Koike Hiroyuki, Matsuzaki Ibu, Iwahashi Yoshifumi, Warigaya Kenji, Fujimoto Masakazu, Ono Kazuo, Urata Youji, Kohjimoto Yasuo, Hara Isao, Murata Shin-ichi, Macrocystic ductal adenocarcinoma of prostate: A rare gross appearance of prostate cancer, Annals of Diagnostic Pathology (2016), doi:10.1016/j.anndiagpath.2016.12.002

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Macrocystic ductal adenocarcinoma of prostate: A rare

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gross appearance of prostate cancer

Fumiyoshi Kojima, MD, PhDa, Hiroyuki Koike, MDb, Ibu Matsuzaki, CTa, Yoshifumi

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Iwahashi, MDa, Kenji Warigaya, MDa, Masakazu Fujimoto, MD, PhDa, Kazuo Ono,

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MD, PhDc, Youji Urata, MD, PhDd, Yasuo Kohjimoto, MD, PDb, Isao Hara, MD, PhDb,

Department of Human Pathology, Wakayama medical university, 811-1, Kimiidera,

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Shin-ichi Murata, MD, PhDa.

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Wakayama, 641-8509, Japan.

Department of Urology, Wakayama medical university, 811-1, Kimiidera, Wakayama,

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641-8509, Japan.

Department of Diagnostic Pathology, Japanese Red Cross Wakayama medical center,

4-20, Komatsubaradori, Wakayama, 640-8558. d

Department of Diagnostic Pathology, Japanese Red Cross Kyoto daiichi hospital,

15-749, Honmachi, Higashiyama, Kyoto, 605-0981.

Correspondence to: Shin-ichi Murata, MD, PhD, Department of Human Pathology,

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Wakayama medical university, 811-1, Kimiidera, Wakayama, 641-8509, Japan. Telephone:

+81-73-441-0635,

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+81-73-444-5777,

E-mail:

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FAX:

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[email protected]

Abstract

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Macroscopic cyst-formation by prostatic adenocarcinoma, herein referred to as

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macrocystic prostatic adenocarcinoma (MPA), is extremely rare. To date, no studies of

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prostate cancer performed based on gross cystic appearance have been reported. MPA

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can include various diseases, one of which is cystadenocarcinoma. Several cases of ductal adenocarcinoma exhibiting a macrocystic appearance have recently been

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reported; however, the histological and clinicopathological characteristics of MPAs have yet to be characterized and established. Therefore, we aimed to determine the histological and clinicopathological characteristics of MPA, via a multi-institutional investigation. We discovered five patients with MPA out of 1,559 treated patients (0.32%); all cases were ductal adenocarcinomas. MPA was found to have three growth patterns: Two cases showed a prevalence of exuberant papillary proliferation with a fibrovascular core in the macroscopic multilocular cysts. Two others predominantly exhibited multilocular cysts lined by flat epithelium with foci of low papillae, and the 2

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fifth had a cystic lesion with intracancerous necrosis. Three of the cases showed

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extraprostatic invasion; however, none of the patients experienced recurrence during the

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follow-up period. Each predominant growth pattern tended to exhibit unique clinicopathological characteristics with respect to serum prostate specific antigen level

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and tumor size and location. In conclusion, we demonstrated that MPA is a ductal

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adenocarcinoma that is composed of intracystic exuberant papillary proliferation and flat proliferation with foci of low papillae, both of which might exhibit different

Keywords:

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clinicopathololgical appearances.

prostate,

ductal

adenocarcinoma,

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cystadenocarcinoma

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cystic,

PIN-like,

macrocystic,

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1. Introduction

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Prostatic carcinoma is one of the highest-incidence malignancies and a top cause of

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cancer-related deaths among men, especially in industrialized countries such as Japan

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and Western countries. Clinical diagnosis of prostatic carcinoma is established using serum prostate-specific antigen (PSA) levels, digital rectal examination, transrectal

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ultrasonography, and biopsy. Prostatic carcinoma is usually detected as a solid, hard mass on transrectal ultrasonography and/or digital rectal examination. The majority of prostatic carcinomas are acinar adenocarcinomas, although some rare variants have also been reported [1]. Macroscopic cyst-formation by prostatic adenocarcinoma is an extremely rare condition that exhibits an unusual appearance on urological examinations. Herein, we refer to prostatic adenocarcinomas that form macrocystic appearances as macrocystic prostatic adenocarcinomas (MPAs). To date, no case series of MPAs based on their 4

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gross appearance have been reported. MPA can include various diseases, one of which is

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cystadenocarcinoma [2-9]. Most cystadenocarcinomas are reported in Japan [3-5, 7].

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Cystadenocarcinoma involves multilocular cysts with papillary proliferations and Roman arch structures lined by stratified columnar cells. Its diagnostic criteria and

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prognosis remain unclear owing to its rarity. Additionally, several cases of ductal

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adenocarcinoma presenting a macrocystic appearance have recently been reported [9-12]. Ductal adenocarcinoma, a variant of prostatic adenocarcinoma, usually presents

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with a macroscopically solid, non-cystic appearance as well as microscopically

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proliferated papillary and cribriform structures composed of tall columnar cells with a

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pseudostratified nucleus. Typical ductal adenocarcinoma often shows aggressive behavior and results in poor overall survival that is similar to that observed with acinar

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adenocarcinoma with a grade group 4. In this study, we aimed to determine the histological and clinicopathological characteristics of MPA through a multi-institutional investigation.

2. Materials and methods 2.1. Study design We reviewed macroscopic findings of 1,559 surgically resected prostatic

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adenocarcinomas treated at three institutions in Japan between 2004 and 2015. We

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retrieved five MPAs from the pathology archives of these hospitals, and obtained

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clinical data from the patients’ medical records. 2.2. Histological and immunohistochemical examinations

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We examined formalin-fixed, paraffin-embedded, and hematoxylin-eosin (HE)-stained

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tissue samples, prepared from whole specimens of resected prostates under light microscopy. Additionally, we performed immunohistochemical staining using standard

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procedures with a Nichirei Histostainer (Nichirei, Tokyo, Japan). The primary

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antibodies used in this study are listed in Table 1. Antigen retrieval was performed using

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a citrate buffered warm bath (pH 6) using the following antibodies: p63, CK-HMW, AMACR, PAX8, and MUC6. We also pretreated the samples in heat processor solution

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(pH 9, Nichirei, Tokyo, Japan) for ERG. The institutional ethical review board of our institution approved this study (No. 1758).

3. Results 3.1. Clinical features We found five cases of MPA from among 1,559 resected prostatic adenocarcinomas (0.32%) (Table 2). The patients were between 64 and 77 years of age, with an average

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age of 70.8 years. Serum PSA levels ranged from 2.27 to 105.43 ng/mL. In all cases,

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postoperative serum PSA levels were below 0.03 ng/mL. Preoperative needle biopsy

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examinations were performed, but definitive pathological diagnoses of adenocarcinoma were not achieved in two cases (patients 1 and 2) until specimens were obtained via

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transurethral resection. None of the patients experienced recurrence during the

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follow-up period of 6–76 months (average: 42.6 months). 3.2. Histological findings

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3.2.1. Macroscopic findings

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The tumor sizes ranged between 1.0 to 5.0 cm; those of patients 1 and 2 were located

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in the periurethral region (Fig. 1) and central zone, respectively, while those of patients 3, 4, and 5 (Figs. 2 and 3) were in the peripheral zone. The tumor of patient 1 invaded

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the urinary bladder (Fig. 1). The lesions in the others patients localized in the prostate (Figs. 2 and 3). The tumors of patient 1 and 2 included intracystic nodules; the cyst of patient 2 contained a bloody fluid. The tumor of patient 5 resembled a hematoma (Fig. 3). 3.2.2. Microscopic findings The histological findings of all MPAs were consistent with ductal adenocarcinoma. Two MPA cases (patients 1 and 2) showed a predominance of papillary proliferation

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with a fibrovascular core in the macroscopic multilocular cysts, as well as exuberant

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proliferation occupying the cystic space (Fig. 1). The tumors in two other cases (patients

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3 and 4) formed macroscopic multilocular cysts with a flat luminal surface as well as foci of low papillary growths with a fibrovascular core (Fig. 2). The MPAs of patients 3

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and 4 did not have exuberant papillary proliferation; patient 3 had a small area of

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papillary growth similar to that of patients 1 and 2 (Fig. 2). The final case (patient 5) was ductal adenocarcinoma with intracancerous necrosis and a hemorrhaging cystic

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lesion (Fig. 3). Two cases (patients 1 and 3) showed acinar adenocarcinoma, grade

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group 1 (Gleason score 3 + 3 = 6), but were separately distributed and distant from each

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other. However, patient 5 exhibited intermingled ductal and acinar adenocarcinoma, grade group 5 (Gleason score 4 + 5 = 9; mixed acinar and ductal adenocarcinoma),

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where the former occupied 40% of the area of the carcinoma. All MPA cases were composed of amphophilic tall columnar cells with enlarged oval nuclei showing pseudostratified alignment. These nuclei showed increased fine granular chromatin and enlarged nucleoli (Fig. 4A). The cyst-lining cells showed atypia that was similar to that of the papillary region (Fig. 4B); some cysts were lined by foamy cytoplasmic cells (Fig. 4C). In patient 5, viable ductal component cells showed a higher nuclear/cytoplasmic ratio, and the extent of nuclear atypia was relatively greater than in

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the other patients (Fig. 4D).

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The MPA cases in this study often revealed invasion to the extraprostatic tissue such as

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the urinary bladder (patient 1), seminal vesicle (patient 2), and periprostatic connective tissue (patient 3) that progressed to pT3 and pT4 according to the 2010 American Joint

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Committee on Cancer staging system [13]. The resection margins in all cases were

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tumor-free. 3.2.3. Immunohistochemical findings

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Immunohistochemical analysis did not detect basal cells in any of the cases, as

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determined by staining for CK34bE12 (Fig. 5A and 5B) and p63. All cases were

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positive for AMACR (Fig. 5C and 5D) and PSA. The proportion and intensity of PSA staining were variable. Of note, all cases were negative for ERG. Papilla-forming cells

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and cyst-lining cells in all cases were negative for the mesonephric marker PAX8 and for the seminal vesicle/ejaculatory duct marker MUC6.

4. Discussion Prostatic carcinomas usually form solid masses, and macrocystic features are extremely rare; their incidence rate has yet to be reported. In this study, the incidence of MPA was only 0.32% among 1,559 resected prostatic adenocarcinoma cases. As

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described above, all our patients’ MPAs were ductal adenocarcinoma that had one of the

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following predominant growth patterns: exuberant papillary proliferation, flat

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proliferation with foci of low papillae, and intracancerous necrosis. Each predominant growth patterns tended to exhibit unique pathological characteristics, whether of

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preoperative PSA levels, tumor sizes, or tumor locations. The serum PSA levels in the

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two cases of flat proliferation with foci of low papillae (2.27 and 8.6 ng/mL, respectively) were lower than in the other cases (105.43, 31.62, and 14.48 ng/mL,

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respectively). The tumor sizes in cases of predominance of exuberant papillary

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proliferation were larger than in the others. The two tumors of flat proliferation

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predominance with foci of low papillae were located in the peripheral zone, whereas those with exuberant papillary proliferation predominance were located in the

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periurethral region in a manner resembling classical pure ductal adenocarcinoma. We have summarized previously published cases of cystic prostatic carcinoma, including cystadenocarcinoma and ductal adenocarcinoma, in Table 3. In one of these studies, Paner, et al. proposed that cystadenocarcinoma was identical to ductal adenocarcinoma with cystic appearance (cystic ductal adenocarcinoma) [9]. In fact, all five cases in our study were pure ductal adenocarcinoma or mixed acinar-ductal adenocarcinoma. Since some descriptions of papillary cystadenocarcinoma or cystic

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ductal adenocarcinoma in the literature are very similar to the histological features

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observed in our patients [4, 8, 9, 11, 14], we infer that cystic ductal adenocarcinomas

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comprise a considerable proportion of cases previously reported as cystadenocarcinoma. The high incidence of ductal adenocarcinoma is very characteristic of MPAs; pure

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ductal adenocarcinomas comprise only 0.40.8% of all prostatic carcinomas, while

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mixed acinar-ductal adenocarcinomas comprise 5% [15]. Paner et al. classified cystadenocarcinoma into giant multilocular and microscopic

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types according to their clinical presentations [9]; these appeared to be similar to our

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cases in which either exuberant papillary proliferation or flat proliferation with foci of

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low papillae were predominant. We found a minor component with exuberant papillary growth extending to the flat proliferative area with low papillae, and speculated that the

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two morphologies belonged to the same tumor type but with differing growth patterns and clinicopathological features. The locations of the cases with exuberant papillary growth were different from those of multilocular cystadenocarcinomas as described by Paner et al., which were located in the peripheral zone. Investigations of additional cases are required for a better understanding of these particular clinicopathological features. Paner et al. did not describe the biological behavior of cystadenocarcinomas; because

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of their short follow-up duration, there were no recurrences in their study. Although we

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had longer follow-up durations in our study, there were no signs of recurrence in any of

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our patients despite frequent extraprostatic invasion. Considering our study as well as previous series, including cases with variability in Gleason scores and stages (Table. 3),

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MPA has the propensity to invade beyond the prostate in a manner similar to

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conventional ductal adenocarcinoma. However, MPA may carry a favorable clinical course such as PIN-like ductal adenocarcinoma [16].

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Preoperative needle biopsy failed to diagnose adenocarcinoma in two patients (1 and

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2) with exuberant papillary growth out of the five MPA cases; additional transurethral

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resection examination was therefore required. We considered that the samples obtained from the area between the periurethral region and central zone were insufficient for

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diagnosis. In that respect, we posited that it is difficult to differentiate between ductal adenocarcinoma with flat proliferation that does not exhibit recognizable components and high-grade PIN by using needle biopsy, since the glands or cysts have flat smooth contours with relatively mild nuclear atypia compared to those of high-grade PIN with conspicuous nucleoli. For example, in patient 3, we observed the margin of a flat luminal surface cyst with focal papillae (Fig. 6A). The flat luminal surface of the cyst, monotonous

cytologic

appearance,

and

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nuclear

atypia

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immunohistochemistry for confirmation (Fig. 6B).

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Generally, needle biopsies are not directed at cysts, however, it may be useful to

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acquire samples from such cysts if prostate cancer is not detected using standard procedures, and to perform repeat biopsies on clinical suspicion of MPA despite its

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rarity. In biopsies of cystic lesions, differential diagnoses should be considered in

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addition to cystadenocarcinoma (cystic ductal adenocarcinoma) and high-grade PIN as follows: non-neoplastic cysts including prostatic utricle, ejaculatory duct, prostatic

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retention, infectious, and hemorrhagic cysts; and neoplastic cyst that encompass

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cystadenoma [5, 6, 8, 17, 18]. Fortunately, differentiating these lesions histologically is

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usually straightforward; however, two caveats must be considered. First, hemorrhagic cysts may harbor adenocarcinomas, particularly ductal adenocarcinomas that often

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necrotize. Second, despite being extremely rare, cystadenomas also comprise flat epithelium without atypia. It is difficult to differentiate between cystadenoma and ductal adenocarcinoma with flat proliferation using only HE staining; however, the identity of basal cells can be confirmed by immunohistochemistry for correct diagnosis. In conclusion, we found that all MPA cases examined in our study were ductal adenocarcinomas, and had growth patterns exemplified by exuberant papillae, flatness with foci of papillae, or intracancerous necrosis. MPA appears to have an invasive

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nature similar to conventional ductal adenocarcinoma, but it is not yet clear if its

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aggressiveness matches that of ductal adenocarcinoma. Further studies are warranted to

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understand the detailed histological and clinicopathological characteristics of MPAs, and to establish a diagnostic method and clinical treatment protocol for this rare prostate

Compliance with Ethical Standards

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Conflicts of interest: none.

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cancer.

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Funding: This research did not receive any specific grant from funding agencies in the

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public, commercial, or not-for-profit sectors. Informed consent: The present study was exempted from review by the Institutional

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Review Board of Wakayama Medical University (No 1758).

Color is used for online only.

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[1]

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adenocarcinoma. Pathology 2010; 42(4), 319-324.

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Figure Legends

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Fig. 1. Macrocystic prostatic adenocarcinoma with exuberant papillary growth (patient 1). A) The arrowhead shows a macrocystic lesion in the periurethral region, while the

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arrow indicates tumor invasion into the urinary bladder. B) Loupe view shows a papillary growth pattern with a fibrovascular core in the cyst. C) The lesion is covered

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by pseudostratified tall columnar epithelium with enlarged oval nuclei and amphophilic

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cytoplasm (low-power magnification [×40]).

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Fig. 2. Macrocystic prostatic adenocarcinoma with a flat luminal surface and low

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papillae (patient 3). A) Macroscopically, a multilocular cystic lesion is located in the right lobe of the peripheral zone (arrowhead). B) Loupe view shows the bulk of the

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adenocarcinoma presenting as a multilocular cyst. Furthermore, a small proportion of

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exuberant papillary growth extending to the flat growth area with low papillae is observed (arrow). C) On low-power view (magnification: ×40), the cyst is lined mainly

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by flat epithelium with foci of low papillae composed of tall columnar cells.

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Fig. 3. Macrocystic prostatic adenocarcinoma with intracancerous necrosis (patient 5).

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A) Macroscopically, a hematoma is visible on the right side of the apex. B) Loupe view shows that the lesion is necrotic, and hemorrhage is present. C) The main portion of the

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tumor is necrotic with visible hemorrhage (magnification: ×40).

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Fig.4. High power magnification of macrocystic prostatic adenocarcinoma (MPA)

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(magnification: ×200 for A, B; ×400 for C, D). A) In the exuberant papillary growth area (patient 1), the adenocarcinoma is composed of amphophilic tall columnar cells

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and pseudostratified enlarged oval-shaped nuclei containing fine granular chromatin and

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mildly enlarged nucleoli. B) In flat growth areas and low papillae (patient 3), cysts with low papillae are lined by cuboidal-to-columnar cells. The nuclear findings resemble

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those of the exuberant papillary growth area. C) In the small portion of the MPA with

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exuberant papillary growth (patient 2), cysts are lined by foamy cytoplasmic cells. D)

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Around the necrotic area (patient 5), viable tumor cells have higher nuclear/cytoplasmic ratios and more significant nuclear atypia compared to those of the other growth

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patterns.

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Fig. 5. Immunohistochemical staining of macrocystic prostatic adenocarcinoma

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(original magnification: ×100 for A and C; ×200 for B and D). A, B) Tumors are negative for cytokeratin (high molecular weight) in the exuberant papillary growth area

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(A) and flat growth area with low papillae (B). Tumor cells are positive for

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growth area with low papillae (D).

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alpha-methylacyl CoA racemase in the exuberant papillary growth area (C) and flat

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Fig. 6. Needle biopsy of macrocystic prostatic adenocarcinoma (patient 3). A)

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Hematoxylin/eosin-stained sample showing flat atypical epithelium with low papillae. B) The sample subjected to immunohistochemistry staining for cytokeratin

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(CK34ßE12); no basal cells are present beneath the atypical epithelium (magnification:

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×100).

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Clone

Dilution

P63

4A4, mouse monoclonal antibody

Dako, Tokyo, Japan

1:200

CK-HMW

34bE12, mouse monoclonal antibody

Dako, Tokyo, Japan

1:200

AMACR

rabbit monoclonal antibody

Dako, Tokyo, Japan

1:500

PSA

ER-PR8, mouse monoclonal antibody

Dako, Tokyo, Japan

1:100

ERG

EP111, rabbit monoclonal antibody

Nichirei, Tokyo, Japan

ready-to-use

PAX8

rabbit polyclonal antibody

Proteintech, Tokyo, Japan

1:200

MUC6

CLH5, lyophilized mouse monoclonal antibody

Leica, Tokyo, Japan

1:200

AMACR Abbreviations:

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Antibody

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Source

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Table 1. Primary antibodies used for immunohistochemistry in this study

CK-HMW, cytokeratin high molecular weight; AMACR, alpha methylacyl CoA racemase; PSA, prostate specific

antigen; ERG, erythroblast transformation-specific-related gene; PAX8, paired box 8; MUC6, mucin-6.

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Age (years)

75

68

Preoperative PSA (ng/mL)

105.43

31.62

Postoperative PSA (ng/mL)

0.02

Site

periurethra

Size (cm)

5.0 × 4.0 × 3.0

4.0 × 3.0 × 4.0

Histological growth characteristic

exuberant pap

exuberant pap

Grade group (Gleason score)

4 (4 + 4 = 8)

pT

4

EPE (location)

urinary bladder

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Follow-up (month)

4

5

77

70

64

2.27

8.6

14.48

<0.01

<0.01

<0.01

<0.01

CZ

PZ

PZ

apex

2.0 × 1.0 × 2.5

1.0 × 0.5 × 0.5

1.0 × 1.0 × 1.5a

flat with foci of low

flat with foci of

papilla

low papilla

4 (4 + 4 = 8)

4 (4 + 4 = 8)

4 (4 + 4 = 8)

5 (5 + 4 = 9)

3b

3a

2a

3a

seminal vesicle

periprostatic tissue

-

periprostatic tissueb

-

-

-

-

+c

1 (3 + 3 = 6)

-

1 (3 + 3 = 6)

-

5 (4 + 5 = 9)

15

73

6

43d

76

MA N

TE D

CE P

AC

acinar adenocarcinoma

3

CR

1

US

Case

Grade group (Gleason score) of combined

T

Table 2. Clinicopathological findings of macrocystic prostatic adenocarcinoma

necrosis

Abbreviations: PSA, prostatic specific antigen; PZ, peripheral zone; CZ, central zone; pap, papillary; EPE, extraprostatic extension; RM, resection margin. a

The size was of the ductal adenocarcinoma component of the mixed acinar-ductal adenocarcinoma

b

Acinar component invaded into the extraprostatic tissue.

cTh

resection margin was positive in the acinar component.

dCase

4 was lost follow-up.

30

AC

CE P

TE D

MA N

US

CR

IP

T

ACCEPTED MANUSCRIPT

31

ACCEPTED MANUSCRIPT

Table 3. Previously reported cases of macrocystic carcinoma, including cystadenocarcinoma and cystic ductal adenocarcinoma. Histological diagnosis

Retrovesical Retrovesical Posterior Retrovesical Retrovesical Right lobe Posterior Left lobe Bladder neck PD sup ver W/A P Retrovesical Retrovesical Retrovesical Left lobe Perirectal NA P Retro/para PZ PZ PZ PZ PZ PZ

12 × 8 × 8 10 × 10 4.5 NA NA 2 NA 1.1 × 1.5 × 1.8 NA NA 7 NA 9×9×7 up to10 5 12 NA 7.5 6.5 × 5.0 × 5.0 16 8.7 NA 3.0 1.8 NA

Pap CA Muc Ad Ad with EM Pap CA Ad Ad Anaplastic cystic ca Ad Pap CA DA Ad DA Pap CA Pap CA Pap CA CA CPA Mixed AA with DA Mixed DA DA DA DA DA

US

CR

IP

T

Size (cm)

MA N

71 63 68 66 68 65 34 80 64 49 64 75 69 62 91 76 68 61 65 62 82 68 69 48 62

Main location

TE D

1 [2] 2 [19] 3 [20] 4 [3] 5 [21] 6 [18] 7 [22] 8 [23] 9 [4] 10 [14] 11 [24] 12 [25] 13 [5] 14 [6] 15 [7] 16 [8] 17 [26] 18 [10] 19 [11] 20 [9] 21 [9] 22 [9] 23 [9] 24 [9] 25 [9]

PSA (ng/mL) NA NA 32 elevated 92 1200 NA 272 5.3 0.9 2.9 38.44 91 8.9 325 NA NA 18.1 3.5 171 8.6 4.2 10.19 3.53 8.04

CE P

Age

AC

Case

32

Exp inv

OP/RM

f/u (month)

NA T, epi NA perirectal NA bone meta NA NA bladder bone meta Bladder neck NA NA bladder perirectal NA Ex, Sv, LN Ex Ex, LN Ex Ex

NA +/NA +/NA +/+ NA NA +/NA +/+/NA +/+/+ +/NA +/NA +/+/+ +/NA +/NA +/NA +/NA +/+

NA 8, NED NA 12, NED 1.5, AWD NA NA 6, AWD NA NA 8, DOD 10, AWD 12, NED 24, NED 41, NED 23. NED NA 8, NED 12, NED 21, DOD 7, NED 15, NED 14, NED 3, NED NA

ACCEPTED MANUSCRIPT

67 74

4.9 85.7

PZ Pelvic cavity

0.7 12

AA DA

T

26 [9] 27 [12]

B, PPT, sv, BW, apd

+/NA +/NA

1, NED 10, NED

IP

Abbreviations: PSA, preoperative prostatic specific antigen; Exp inv, extraprostatic invasion; OP/RM, surgical operation/resection margin; f/u, follow-up;

CR

NA, not available; Pap, papillary; CA, cystadenocarcinoma; Muc, mucinous; Ad, adenocarcinoma; T, testis; epi, epididymis; NED, no evidence of disease; posterior, posterior to prostate; Ad with EM, adenocarcinoma with an endometrioid pattern; AWD, alive with disease; Right lobe, right lobe of prostate; meta,

US

metastasis; ca, carcinoma; Left lobe, left lobe of prostate; B, bladder; PD sup ver, prostatic duct superior to the verumontanum; DA, ductal adenocarcinoma;

MA N

W/A, within and around; P, prostate; DOD, dead of disease; CPA, cystic prostatic adenocarcinoma; Ex, extraprostatic tissue; sv, seminal vesicle; LN, lymph

AC

CE P

TE D

node; Retro/para, retroprostatic and pararectal; AA, acinar adenocarcinoma; PPT, periprostatic tissue; BW, bowel wall; apd, appendix vermiformis.

33

T

ACCEPTED MANUSCRIPT

CR

IP

Highlights Macroscopically cyst-forming prostatic adenocarcinoma (MPA) is an extremely rare.

2

The high incidence of ductal adenocarcinoma is very characterstic of MPA.

3

MPA includes three growth patterns: papillary, flat, and necrotic.

4

MPA shows frequent extraprostatic growth, but may be good prognosis.

AC

CE P

TE D

MA N

US

1

34