Polish Journal of Pathology
 
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A case of prostatic adenocarcinoma with Paneth cell-like appearance

Yasuhiro Nakamura, Fumiyoshi Fujishima, Mika Watanabe, Shinji Taniuchi, Kazuyuki Ishida, Shigeto Ishidoya, Yoichi Arai, Hironobu Sasano

Pol J Pathol 2011; 1: 60–64
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Introduction

Paneth cell-like appearance of prostatic adenocarcinoma is considered to be a feature of neuroendocrine differentiation characterized by carcinoma cells with prominent eosinophilic cytoplasmic granules [1-8]. Herein, we report a case of prostatic adenocarcinoma admixed with Paneth cell-like neuroendocrine differentiation localized next to with conventional adenocarcinoma evaluated by using the extensive mapping analysis and immunohistochemical method.

Case report

A 55-year-old Japanese man appeared to have a high serum prostatic-specific antigen (PSA) level (17.8 ng/ml) in his regular physical examination. A digital examination and needle biopsy of the prostate were performed. A subsequent histological examination revealed moderately-well differentiated adenocarcinoma. The patient underwent radical prostatectomy at the Tohoku University Hospital.

The extensive mapping analysis of the resected specimens revealed the diffuse spread of the tumour in the bilateral lobes (Fig. 1). In addition, tumour tissues consisted of two different types of carcinoma:

• well to moderately differentiated acinar adenocarcinoma with numerous crystalloids, showing perineural and vascular invasion, and extending through the prostatic capsule (Fig. 1 and 2);

• glandular, cribriform, trabecular and patchy isolated structures formed by round to pyramidal cells with markedly eosinophilic granular cytoplasm (Fig. 1 and 3).

The latter component was consistent with pathological features of Paneth cell-like carcinoma cells in the prostate gland [1-8]. Immunohistochemical analysis demonstrated that these Paneth cell-like carcinoma cells were positive for chromogranin A, synaptophysin, and negative for androgen receptor (AR) (Fig. 4).

Discussion

Prostatic pathology with Paneth cell-like appearance was considered rare in both benign and malignant prostatic diseases [1-8]. Paneth cell-like changes were reported to be detected in 10% of prostatic adenocarcinomas and were usually composed of only rare foci of scattered cells and/or small clusters of tumour cells [5]. Prostatic adenocarcinoma with Paneth cell-like features has been previously detected either in Gleason pattern 3, Gleason pattern 4 or Gleason pattern 5, which are consistent with the present case [6].

Eosinophilic granules in Paneth cell-like appearance were reported negative for lysozyme, making them distinct from the true Paneth cells of the small intestine [1, 4-6]. Prostatic adenocarcinoma with Paneth cell-like appearance was reported to be diffusely positive for neuroendocrine markers such as chromogranin, synaptophysin and serotonin, consistent with our present report [6]. Neuroendocrine cells (NECs) in prostatic adenocarcinoma are generally considered a feature of androgen insensitivity due to the absence of ARs as shown in our present case [6]. Results of previous studies have suggested that NECs may play an important role in prostatic cancer development and progression through actions of various peptides produced and secreted in these cells in a paracrine manner via an androgen-independent pathway [6, 9-11]. However, prostatic adenocarcinoma with neuroendocrine differentiation ranged from focal NECs in conventional adenocarcinoma, to carcinoid tumour and small cell carcinoma/poorly differentiated neuroendocrine carcinoma [6, 12]. Tamas et al. previously suggested that in cases with Paneth cell-like NECs, only the conventional adenocarcinoma component should be assigned a Gleason score [6]. In addition, they also proposed that in cases in which the entire tumour is composed of Paneth cell-like cells with the absence of glandular differentiation, the tumours should not be assigned a Gleason score and a comment should be provided to urologists as to the generally favourable prognosis of this morphologic pattern of neuroendocrine differentiation [6]. However, it awaits further examination to clarify the association with the presence of prostatic adenocarcinoma with Paneth cell-like appearance and eventual clinical outcome for the patients.

In our case, the tumour area formed by carcinoma cells with Paneth cell-like appearance occupied a small area and was separately located from the areas of conventional acinar adenocarcinoma. We could not find previous studies describing in detail the colocalization patterns of these two different types of carcinoma cells. The mapping of the resected prostate glands requires labour intensiveness but an examination of the entire tissue of the surgical prostatic specimen is very important in order to detect the presence of carcinoma cells associated with different characters.

In summary, we report a case of prostate carcinoma demonstrating Paneth cell-like neuroendocrine differentiation coexisting with conventional adenocarcinoma. Pathologists should carefully examine whether such a small area of carcinoma with neuroendocrine differentiation exists together with conventional acinar adenocarcinoma regarding possible association with resistance to hormone therapy.

References

 1. Kuroda N, Katto K, Shiotsu T, et al. Prostatic adenocarcinoma with Paneth cell-like change. APMIS 2007; 115: 857-858.  

2. Weaver MG, Abdul-Karim FW, Srigley J, et al. Paneth-cell like change of the prostatic gland. A histological, immunohistochemical, and electron microscopic study. Am J Surg Pathol 1992; 16: 62-68.  

3. Frydman CP, Bleiweiss IJ, Unger PD, et al. Paneth cell-like metaplasia of the prostatic gland. Arch Pathol Lab Med 1992; 116: 274-276.  

4. di Sant'Agnese PA. Neuroendocrine differentiation in prostatic adenocarcinoma does not represent true Paneth cell differentiation. Hum Pathol 1994; 25: 115-116.  

5. Adlakha H, Bostwick DG. Paneth cell-like change in prostatic adenocarcinoma represents neuroendocrine differentiation. Hum Pathol 1994; 25: 135-139.  

6. Tamas EF, Epstein JI. Prognostic significance of Paneth cell-like neuroendocrine differentiation in adenocarcinoma of the prostate. Am J Surg Pathol 2006; 30: 980-985.  

7. Haratake J, Horie A, Ito K. Argyrophilic adenocarcinoma of the prostate with Paneth cell-like granules. Acta Pathol Jpn 1987; 37: 831-836.  

8. Islam AM, Kato H, Hayama M, et al. Prostatic adenocarcinoma with marked neuroendocrine differentiation. Int J Urol 2001; 8: 412-415.  

9. Bankhoff H. Neuroendocrine differentiation in human prostate cancer. Morphogrnesis, proliferation and androgen receptor status. Ann Oncol 2001; 12 (Suppl 2): S141-144.

10. Grobholz R, Griebe M, Sauer CG, et al. Influence of neuroendocrine tumor cells on proliferation in prostatic carcinoma. Hum Pathol 2005; 36: 562-570.

11. Krijnen JL, Bogdanowicz JF, Seldenrijk CA, et al. The prognostic value of neuroendocrine differentiation in adenocarcinoma of the prostate in relation to progression of disease after neuroendocrine therapy. J Urol 1997; 158: 171-174.

12. di Sant'Agnese PA, Cockett AT. Neuroendocrine differentiation in prostate malignancy. Cancer 1996; 78: 357-361.

Address for correspondence

Yasuhiro Nakamura , MD

Department of Pathology

Tohoku University School of Medicine

2-1 Seiryo-machi, Aoba-ku, Sendai

980-8575 Japan

tel. +81-22-717-8050

fax +81-22-717-8051

e-mail: yasu-naka@patholo2.med.tohoku.ac.jp
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