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Year : 2016  |  Volume : 59  |  Issue : 2  |  Page : 203-205
Pseudopapillary prostatic adenocarcinoma: A diagnostic pitfall for pathologists

1 Department of Pathology, Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India
2 Department of Uro-Oncology, Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India

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Date of Web Publication9-May-2016


Prostatic adenocarcinoma and urothelial carcinoma are common tumours seen in elderly patients. They both act as a close differential diagnosis for each other clinically as well as histologically. Various morphological patterns have been described in prostatic adenocarcinomas. However, pseudopapillary pattern was not described until recently a paper which described seven such cases. These tumours mimic urothelial carcinoma as the papillary pattern is usually seen in urothelial carcinoma and may act as a pitfall for the diagnosing pathologists. As both the tumours are treated with different therapeutic protocol it is necessary to differentiate the two and hence the pathologist should be aware of this morphological variant of prostatic carcinoma. Critical histological review and immunohistochemical examination is helpful to make the diagnosis. Here we discuss one such case of pseudopapillary prostatic adenocarcinoma mimicking urothelial carcinoma with a brief review of histological and immunohistochemical examination useful to distinguish the two tumours.

Keywords: Adenocarcinoma, prostate, pseudo-papillary, urothelial

How to cite this article:
Verma A, Menon S, Bakshi G, Desai S. Pseudopapillary prostatic adenocarcinoma: A diagnostic pitfall for pathologists. Indian J Pathol Microbiol 2016;59:203-5

How to cite this URL:
Verma A, Menon S, Bakshi G, Desai S. Pseudopapillary prostatic adenocarcinoma: A diagnostic pitfall for pathologists. Indian J Pathol Microbiol [serial online] 2016 [cited 2023 Oct 2];59:203-5. Available from:

   Introduction Top

Prostatic adenocarcinoma represents 9.7% of cancer in men and is treated with surgical excision and/or hormonal therapy while urothelial cancer accounts for 3.2% of all cancers and are treated with surgical resection and chemotherapy. Hence, it is paramount importance to differentiate prostatic carcinomas from urothelial carcinomas.[1] Moreover, the prognosis of urothelial carcinoma involving the prostate is significantly different than detection of two separate primaries in bladder and prostate.[2] A poorly differentiated high-grade tumor may pose a morphological challenge to differentiate between the two. Morphologically, formation of papillary and pseudopapillary structures favors urothelial carcinoma. However, recently seven cases of conventional prostatic adenocarcinoma with pseudopapillary features have been described.[3] Herein, we describe one such case of prostatic adenocarcinoma, which had prominent papillary and inverted papillary growth pattern.

   Case Report Top

A 54-year-old male, a known case of prostatic adenocarcinoma was referred to our institute with lower urinary tract symptoms of decreased urinary stream since 3 months. He was a diagnosed to have prostatic adenocarcinoma on a needle biopsy 3 years before to current referral with a modified Gleason score of 3 + 5 = 8. He was on oral anti-androgen therapy and had also undergone bilateral orchidectomy. On digital rectal examination, the patient had a grade 3 hard prostatomegaly. Computerized tomographic scan done revealed metastasis in abdominal lymph nodes, liver, and lungs, and the bone scan revealed sclerotic metastasis in pubic bone. The total serum prostate-specific antigen (PSA) level was 663.24 ng/mL. Cystoscopy showed a normal urethra and large irregular prostatic lobes obliterating the prostatic urethra and extending to the base of the bladder. A transurethral resection of the prostate (TURP) was performed and the tissue was sent for histopathological examination.

Histological examination of the TURP showed a malignant tumor arranged in a papillary and pseudopapillary pattern with a central fibrovascular core resembling urothelial carcinoma. Foci with prominent inverted papilloma-like growth pattern were also seen. In few areas, the tumor was arranged in solid sheets. On higher power, the cells had pale eosinophilic cytoplasm. The nuclei were monomorphic with prominent nucleoli. Mitotic figures were frequent including atypical mitosis. No definite areas of glandular/ductal differentiation or microacinar formation were seen. No benign prostatic glands were identified. Morphological pattern of papillae including inverted papillae strongly favored a high-grade urothelial carcinoma over a high-grade prostatic adenocarcinoma [Figure 1]. However, on immunohistochemistry, the tumor strongly expressed prostatic markers PSA and metabolic marker alpha methyl acyl CoA racemase (AMACR), seen in prostate adenocarcinomas while it was negative for urothelial markers p63, cytokeratins-7 (CK7), and high molecular weight cytokeratin (HMWCK) [Figure 2]. There were no morphological changes to suggest any hormonal related effect on the tumor morphology. Hence, a diagnosis of conventional prostatic adenocarcinoma with Gleason score 5 + 5 = 10 was rendered. Currently, the patient is on palliative radiotherapy and chemotherapy.
Figure 1: Pseudopapillary prostatic adenocarcinoma showing fragments which appear papillary (a; H and E, ×40), inverted papilloma like pattern (b; H and E, ×100), pseudopapillary broad based cores lined by tumor cells (c; H and E, ×100). Focal areas of solid pattern with overlying urothelium(d; H and E, ×100)

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Figure 2: Indirect immunoperoxidase immunohistochemistry showing immunoreactivity to alpha methyl acyl CoA racemase (a) and prostate specific antigen (b) and negative tumor staining with cytokeratins-7 (c) and high molecular weight cytokeratin (d)

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   Discussion Top

Both urothelial carcinomas and prostatic carcinomas are seen in elderly patients. Cystoscopically and clinically it may be difficult to differentiate between prostatic carcinomas and urothelial carcinomas of the urinary bladder neck.[1],[3] As there is a fundamental difference in treatment protocol between the two carcinomas, it is imperative to differentiate the two. However, both the tumor may occur either synchronously or metachronously and in rare circumstances a collision tumor can be seen.[3]

Histological examination is helpful in differentiating the two tumors. Even poorly differentiated carcinomas can be differentiated morphologically. Urothelial carcinomas have more commonly a papillary pattern with an amphophilic cytoplasm and pleomorphic hyperchromatic nuclei. On the other hand, prostatic cancers have a more uniform morphology with a pale eosinophilic cytoplasm, monomorphic nuclei, and prominent nucleoli.[1] Areas of glandular differentiation and microacinar formation favor a tumor of prostatic origin. However at times on morphology, a poorly differentiated tumor would be difficult to differentiate and immunohistochemistry is necessary in such cases. Our case highlights the rare occasion, wherein a prostatic adenocarcinoma may mimic a papillary urothelial carcinoma.

Pseudopapillary pattern has been traditionally associated with urothelial carcinomas and was an important finding to distinguish it from prostatic adenocarcinomas. Recently, Gordetsky and Epstein in a review of high-grade prostatic adenocarcinoma identified seven cases of prostatic adenocarcinoma with pseudopapillary architecture. Some of their patients' had a history of prostatic adenocarcinoma while others did not. In all seven cases, similar to our case, a differential diagnosis of urothelial carcinoma on morphology was considered. Immunohistochemistry was useful in distinguishing these tumors.[3] To the best of our knowledge, this is the eighth case of pseudopapillary carcinoma of prostate reported in literature.

Immunohistochemistry must be used in such cases to make the final diagnosis. Various immunohistochemical markers such as GATA3, thrombomodulin, uroplakin III, HMWCK, p63, CK7, and CK20 are useful to make a diagnosis of urothelial carcinomas. GATA3 is a useful and specific marker as it is positive in approximately 90% of urothelial carcinomas including the high-grade tumors and negative in prostatic carcinomas.[4] Uroplakin III is less sensitive as it shows positivity in only 60% of urothelial carcinomas. Thrombomodulin similar to uroplakin III is positive in only 60% of urothelial carcinomas. However, uroplakin III and thrombomodulin are highly specific for being negative in prostatic carcinomas.[5],[6] HMWCK and p63 are highly sensitive for urothelial carcinomas and is seen in 80–90% of cases. Though both can be seen focally in high-grade prostatic adenocarcinomas, rare diffuse p63 positivity has also been reported and probably represents a molecularly distinct type of prostatic adenocarcinomas.[6],[7],[8] Markers such as PSA, prostate-specific membrane antigen, P501S, and NKX3.1 are immunopositive in prostatic adenocarcinomas.[9] PSA, NKX3.1, and P501S are highly specific for prostate and are seen in more than 95% of prostatic adenocarcinomas and are negative in urothelial carcinomas.[5],[10] In the current case, immunohistochemical reactivity to PSA and AMACR with negative urothelial markers CK7, p63, and HMWCK clinched the diagnosis.

Thus, we conclude by re-emphasizing that prostatic adenocarcinomas can rarely have pseudopapillary pattern. The reporting pathologist must have a high degree of suspicion to recognize and report these cases as they have therapeutic implications. The help of immunohistochemistry should always be sought in difficult cases where the morphology is that of a poorly differentiated carcinoma occurring in the bladder neck region.

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   References Top

Eble JN, Sauter G, Epstein JI, Sesterhenn IA Pathology and Genetics of Tumors of the Urinary System and Male Genital Organs. 3rd ed. Lyon: International Agency for on Cancer; 2004.  Back to cited text no. 1
Bruins HM, Djaladat H, Ahmadi H, Sherrod A, Cai J, Miranda G, et al. Incidental prostate cancer in patients with bladder urothelial carcinoma: Comprehensive analysis of 1,476 radical cystoprostatectomy specimens. J Urol 2013;190:1704-9.  Back to cited text no. 2
Gordetsky J, Epstein JI. Pseudopapillary features in prostatic adenocarcinoma mimicking urothelial carcinoma: A diagnostic pitfall. Am J Surg Pathol 2014;38:941-5.  Back to cited text no. 3
Chang A, Amin A, Gabrielson E, Illei P, Roden RB, Sharma R, et al. Utility of GATA3 immunohistochemistry in differentiating urothelial carcinoma from prostate adenocarcinoma and squamous cell carcinomas of the uterine cervix, anus, and lung. Am J Surg Pathol 2012;36:1472-6.  Back to cited text no. 4
Chuang AY, DeMarzo AM, Veltri RW, Sharma RB, Bieberich CJ, Epstein JI. Immunohistochemical differentiation of high-grade prostate carcinoma from urothelial carcinoma. Am J Surg Pathol 2007;31:1246-55.  Back to cited text no. 5
Parker DC, Folpe AL, Bell J, Oliva E, Young RH, Cohen C, et al. Potential utility of uroplakin III, thrombomodulin, high molecular weight cytokeratin, and cytokeratin 20 in noninvasive, invasive, and metastatic urothelial (transitional cell) carcinomas. Am J Surg Pathol 2003;27:1-10.  Back to cited text no. 6
Giannico GA, Ross HM, Lotan T, Epstein JI. Aberrant expression of p63 in adenocarcinoma of the prostate: A radical prostatectomy study. Am J Surg Pathol 2013;37:1401-6.  Back to cited text no. 7
Tan HL, Haffner MC, Esopi DM, Vaghasia AM, Giannico GA, Ross HM, et al. Prostate adenocarcinomas aberrantly expressing p63 are molecularly distinct from usual-type prostatic adenocarcinomas. Mod Pathol 2015;28:446-56.  Back to cited text no. 8
Mhawech P, Uchida T, Pelte MF. Immunohistochemical profile of high-grade urothelial bladder carcinoma and prostate adenocarcinoma. Hum Pathol 2002;33:1136-40.  Back to cited text no. 9
Mhawech-Fauceglia P, Zhang S, Terracciano L, Sauter G, Chadhuri A, Herrmann FR, et al. Prostate-specific membrane antigen (PSMA) protein expression in normal and neoplastic tissues and its sensitivity and specificity in prostate adenocarcinoma: An immunohistochemical study using mutiple tumor tissue microarray technique. Histopathology 2007;50:472-83.  Back to cited text no. 10

Correspondence Address:
Sangeeta Desai
Department of Pathology, Eighth Floor, Annexe Building, Tata Memorial Hospital, Parel, Mumbai - 400 012, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.182020

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