Adenoid cystic carcinoma of the prostate: Case report on a rare entity and review of the literature

Adenoid cystic carcinoma of the prostate: Case report on a rare entity and review of the literature

Pathology – Research and Practice 207 (2011) 391–394 Contents lists available at ScienceDirect Pathology – Research and Practice journal homepage: w...

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Pathology – Research and Practice 207 (2011) 391–394

Contents lists available at ScienceDirect

Pathology – Research and Practice journal homepage: www.elsevier.de/prp

Teaching case

Adenoid cystic carcinoma of the prostate: Case report on a rare entity and review of the literature Arvind Ahuja a , Prasenjit Das a , Narender Kumar a , Ashish Kumar Saini b , Amlesh Seth b , Ruma Ray a,∗ a b

Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi 110029, India Department of Urology, All India Institute of Medical Sciences, New Delhi, India

a r t i c l e

i n f o

Article history: Received 24 July 2010 Received in revised form 15 December 2010 Accepted 28 January 2011 Keywords: Adenoid cystic carcinoma Prostate carcinoma Prostate specific antigen

a b s t r a c t Adenoid cystic carcinoma is an unusual histological variant of prostatic carcinoma. Because of its rarity, the natural history of this tumor is not known. Here we report this rare entity in a 62-year-old man who presented with symptoms of urinary tract obstruction. Digital rectal examination and ultrasonography (USG) showed an enlarged hard nodular prostate. Serum prostate-specific antigen (PSA) and prostatic acid phosphate levels were found to be within the normal range. Transrectal ultrasound-guided 12 core biopsies of prostate showed morphological features of an adenoid cystic carcinoma in 8 cores (bilateral, mid and base) on histopathological examination. Immunohistochemistry performed for PSA on paraffin section was negative. After diagnosis, bilateral orchidectomy was performed, and hormonal therapy was started in the form of androgen receptor blocker. The patient was clinically stable during a limited follow up of six months. © 2011 Elsevier GmbH. All rights reserved.

Introduction Prostate cancer is the most common malignancy in men and the leading cause of mortality and morbidity worldwide. Although conventional acinar adenocarcinoma accounts for the majority of prostatic malignancies, it is important to recognize rare variants, like adenoid cystic carcinoma (ACC), as prognosis of these tumors may vary accordingly. ACC of prostate is a rare entity. This tumor was first reported in salivary gland by Billroth in 1859 [1], who described ACC as a tumor with cribriform, glandular, and basaloid patterns containing mucous material. Besides salivary glands, these tumors have been reported in maxillary antrum, skin, lung, breast, and cervix. Only few case reports and case series of ACC of prostate are available. We report an additional case of prostatic ACC in an elderly patient. Clinical report A 62-year-old man came to the out-patient facility of urology with a 3-month history of obstructive lower urinary tract symptoms. There was no history of hematuria or any other significant previous medical history. Digital rectal examination (DRE) revealed an enlarged hard fixed nodular prostate. Serum PSA level was within normal range (3.9 ng/mL). Due to a suspicious DRE,

∗ Corresponding author. Tel.: +91 11 26594604; fax: +91 11 26588663. E-mail addresses: [email protected], [email protected] (R. Ray). 0344-0338/$ – see front matter © 2011 Elsevier GmbH. All rights reserved. doi:10.1016/j.prp.2011.01.012

trans-rectal ultrasonography (TRUS)-guided routine, 12 core biopsies were taken from the apex, mid gland, and base with the help of biopsy gun (2 cores in each laterally and medially, respectively, on each side) [2]. After diagnosis, due to advanced clinical stage and surgical inoperability (fixed growth in the pelvis), maximum androgen blockade in the form of bilateral orchidectomy and bicalutamide (50 mg OD) was started in the present case. The patient was clinically stable during post-operative period. There was no progression of disease during the 6 months of follow-up. However, the patient was lost to follow up after six months of diagnosis. Histopathological features Biopsies from bilateral, mid, and base regions showed smaller monomorphic tumor cells arranged in a solid basaloid pattern, as well as focally in a cribriform pattern floating in a pool of extracellular mucin (Fig. 1a and b). The tumor cells were small with scant cytoplasm and angulated hyperchromatic nuclei. Focally, the glands were infiltrating prostatic fibromuscular tissue. Perineural invasion was also identified in the sections examined (Fig. 1c). Periodic acid Schiff-alcian blue stain (pH 2.5) stained mucin blue, indicating acidic nature of the mucin (Fig. 1d). Immunohistochemistry with monoclonal antibody for PSA [NovaCastra; 1:100] was negative, while cytokeratin [DAKO; 1:100], smooth muscle actin [NovaCastra; 1:800] (Fig. 2a), and Her2neu [NovaCastra; 1:50] (Fig. 2c) stains showed strong positivity in the tumor cells. Her2neu expression was noted both in the tumor cell cytoplasm and in

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Fig. 1. Photomicrograph showing ACC of prostate with characteristic basaloid and cribriform pattern (a, [H&E] 40×). Small, round basaloid tumor cells with oval hyperchromatic nuclei and surrounding abundant mucin are noted in and around the cribriform glands (b, [H&E] 200×); peri-neural invasion of the tumor cells (c, [H&E] 200×). Special stain shows abundant extracellular acid mucin positive for alcian blue at pH 2.5 (d, [PAS-AB] 400×).

Fig. 2. Tumor cells are showing strong immuno-positivity for SMA (a, [IHC] 400×); positivity for bcl2 in the outer layer of cells (b, [IHC] 400×) and strong cytoplasmic as well as membranous positivity for Her2neu (c, [IHC] 400×) and nuclear positivity for AR (d, [IHC] 400×).

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Table 1 Status of serum PSA (sPSA) and PSA IHC in ACCs. Authors

Year

Age

sPSA

PSA IHC

Denholm et al. [8] Cohen et al. [9] Shindo and Ikeda [10] Terris [11] Minei et al. [12] Iczkowski et al. (19 cases) [3] Present case

1992 1993 1998 1999

28 58 51 63 55 43 43–83 62

Normal Normal Normal NA Mildly raised Normal Normal (except in 2-mildly elevated) Normal

Negative Negative Negative NA NA Negative Positive in only 3 cases (15.7%) Negative

2001 2003 2010

NA: not available.

cell membrane. Bcl2 [NovaCastra; 1:100] (Fig. 2b) stain showed positivity of the outer layer cells of the tumor cell clusters. Androgen receptor [NovaCastra; 1:50] immunohistochemistry showed nuclear positivity of approx. 6% counted in 500 cells at high power (Fig. 2d). CD117 [DAKO; 1:500] was negative. Based on the characteristic morphology and results of immunohistochemistry, a diagnosis of an adenoid cystic variant of prostatic carcinoma was made. Discussion ACC is a rare tumor of prostate. To the best of our knowledge, approximately 50 cases have been reported in English literature. The largest series includes 19 cases reported by Iczkowski et al. [3], who concluded that ACC of the prostate is a tumor with the potential for extraprostatic extension, recurrence, and metastasis. Almost all cases showed either an adenoid or a basaloid pattern. In most of the cases, serum PSA level was normal, and PSA immunostain was negative [3]. On IHC, the tumor cells were positive for high-molecular-weight keratin (clone 34␤E12) and cytokeratin 14, at least focally in all reported cases [3–5]. Accordingly, the cell of origin in ACC was supposed to be the basal cell, while in other carcinomas of the prostate, for example the mucinous carcinoma of prostate arises from the inner secretary epithelium, carcinoids from endocrine cells, and transitional and squamous cell carcinoma from transitional epithelium [6]. The initial diagnosis in such a tumor is based on abnormal digital rectal examination and TRUS, as serum PSA is mostly within normal range or slightly elevated. In our case, serum PSA was also normal. The predominant arrangement, on histopathology, was basaloid pattern, and on IHC, PSA was negative and pancytokeratin was positive. Morphologically, there was abundance of extracellular AB-PAS (pH 2.5)-positive mucin, while in contrast, usual acinar adenocarcinoma lacks myxoid stromal response [7]. Extra-cellular mucin can also be seen in mucinous/colloid carcinomas of prostate, but the histomorphology of the lining epithelium helps to differentiate these two. Considering that in our case there was no tall columnar epithelium with goblet cells, we excluded this possibility. IHC for PSA did not help to differentiate ACC and colloid carcinomas, as PSA is also negative in colloid carcinoma of the prostate, indicating that these variants of prostatic carcinoma do not secrete PSA [7]. Similar examples of PSA expression have also been reported in the earlier literature [3,8–12] (Table 1). The other differential diagnoses of adenoid cystic/basal cell carcinoma of the prostate include benign basal cell hyperplasia and cribriform pattern of acinar adenocarcinoma. Benign basal cell hyperplasia is a lesion that typically occurs in the transition zone of prostate in elderly men, and is frequently associated with benign nodular hyperplasia. In these lesions, the luminal spaces are bounded by secretary cells, and the cribriform architecture does not form large confluent expansive island. Histological features of malignancy-like necrosis, peri-neural invasion, extra-prostatic extension, and stromal response are also not seen. The cribriform pattern of acinar adenocarcinoma is characterized by small and

large back to back infiltrating glands and the formation of lumen by traversing tumor cell bridges. Cells of acinar adenocarcinomas are positive for PSA on immunohistochemistry. The basaloid pattern of ACC of the prostate can often be mistaken for a basaloid variant of squamous cell carcinomas. In the study conducted by Emanuel et al. [13], the authors used p63 immunostain to differentiate these two entities. They found that while p63 shows diffuse immunopositivity in the basaloid variant of SCC, it showed a more compartmentalized pattern of expression in ACCs. Though expression of Her2neu in ACC of salivary glands has been reported, the incidence of expression of this marker protein in prostatic counterpart is rare. An expression of this protein in prostatic ACC makes them susceptible to treatment with Herceptin. In normal acinus, Her2neu has been seen to be expressed only in outer cell layers [14]. Though SMA has been seen to be negative in other reports on ACC, this stain was strongly positive in our case [6]. In our case, immunopositivity for bcl2, SMA, Her2neu, and androgen receptor (AR) was noted in the tumor cells. Androgen suppression is the gold standard, first-line therapy for advanced/metastatic disease [15]. Few studies have shown that AR expression by immunohistochemistry is heterogeneous in prostate cancer, and response to androgen deprivation therapy does not generally correlate with the degree of heterogeneity [16]. In view of advanced clinical stage and surgical inoperability (fixed growth in the pelvis) in the present case, bilateral orchidectomy was performed and hormonal therapy (bicalutamide) was started. Exact prognosis of prostatic ACC is not known due to the scarcity of reported cases. Iczkowski et al. described 19 cases of ACC of prostate. Out of these follow-up was available in 15 cases. Nodal metastasis was noted in 21% of cases. A 5-year metastatic potential ranges from 5–10% in T1/T2 tumor to 50–85% in stage T3/T4 tumor [7]. Conclusion Adenoid cystic carcinoma is a rare subtype of prostate cancer, and a correct diagnosis is important because of its potential for extra-prostatic extension. Initial suspicion of malignancy is difficult as the serum PSA level is not increased. Recognition of this rare entity is important for making accurate histopathological diagnosis. References [1] T. Billroth, Beobachtung uber Gerchwulste der speicheldrusen, Virchow’s Arch. Pathol. Anat. 17 (1859) 357–375. [2] K.K. Hodge, J.E. McNeal, M.K. Terris, T.A. Stamey, Random systematic versus directed ultrasound guided trans-rectal core biopsies of the prostate, J. Urol. 142 (1989) 71–74. [3] K.A. Iczkowski, K.L. Ferguson, D.D. Grier, et al., Adenoid cystic/basal cell carcinoma of the prostate: clinicopathologic findings in 19 cases, Am. J. Surg. Pathol. 27 (2003) 1523–1529. [4] J.K. McKenney, M.B. Amin, J.R. Srigley, et al., Basal cell proliferations of the prostate other than usual basal cell hyperplasia: a clinicopathologic study of 23 cases, including four carcinomas, with a proposed classification, Am. J. Surg. Pathol. 28 (2004) 1289–1298.

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