COW-2022-12

CASE OF THE WEEK

Editor: Mahmut Akgul (akgulm@amc.edu)

2022-12/March 21
Contributors: Laurence Galea, Scott Donnellan

A male patient in his 70s underwent transurethral resection of the prostate.

Quiz

1. What is the correct diagnosis?

a. Prostatic basal cell hyperplasia

b. Urothelial carcinoma

c. Small cell carcinoma

d. Prostatic adenoid cystic (basal cell) carcinoma

e. Prostatic acinar adenocarcinoma

 

2. A subset of cases of this entity harbour rearrangement of which gene?

a. TMPRSS2

b. MAML

c. MYB

d. ALK

e. NTRK

1. d; 2. c

1. Prostatic adenoid cystic (basal cell) carcinoma; 2. MYB (not listed)

The correct diagnosis is prostatic adenoid cystic (basal cell) carcinoma (PACC) composed of a basaloid proliferation with varied architectural patterns. These included large anastomosing solid nests (Figure 1 centre), adenoid cystic/cribriform areas (Figure 2), small solid nests and small tubules (Figure 3). In areas the tumour appeared to infiltrate in between normal prostatic acini (Figure 4). The cells showed high nuclear to cytoplasmic ratios, oval to elongated hyperchromatic nuclei, small nucleoli and small amount of ill-defined amphophilic cytoplasm. The adenoid cystic areas showed punched out lumina containing eosinophilic basement membrane or basophilic mucinous secretion (Figure 2). The basaloid nests were centrally lined by eosinophilic cells. Only rare mitotic figures were identified (less than 1 per mm2). Necrosis, perineural invasion and extraprostatic extension were not seen. No coexisting prostatic adenocarcinoma was identified and the included urothelium was normal. The lesional cells were positive for p63 and 34Be12 and Bcl-2. CK7 was essentially negative apart from rare expression in luminal cells. CK20, NKX3.1, PSA, AMACR, Her-2 and MYB were negative. The Ki-67 proliferation index was approximately 5%.

In contrast to conventional prostatic acinar adenocarcinoma, PACC is thought to be derived from the prostatic basal cells rather than the luminal secretory epithelium and therefore the serum prostate-specific antigen is usually normal unless there is coexisting prostatic adenocarcinoma. Most cases show variable architectural patterns including large and small solid nests, adenoid cystic-like pattern, small tubules and cords of cells. While differentiating PACC from prostatic basal cell hyperplasia (PBCH) can be challenging several features can be useful. These include adenoid cystic pattern, large basaloid nests with necrosis, anastomosing basaloid nests, nests or tubules centrally lined by eosinophilic cells and variable small to medium sized nests with irregular shape, prominent desmoplastic or myxoid stromal response, widely infiltrative pattern into the stroma and between normal prostatic acini and perineural invasion. Extraprostatic extension and seminal vesicle involvement are diagnostic of malignancy though not typically seen in diagnostic specimens.1-4

In keeping with basal cell origin PACC is positive for basal cell markers but these are not useful in distinguishing from PBCH. Strong Bcl-2 and increased Ki-67 proliferation index can help distinguish PACC from PBCH, though the Ki-67 proliferation index can vary widely in PACC. CK7 is negative or expressed in luminal cells and CK20 is negative in PACC1,2 helping to distinguish from urothelial carcinoma, especially given that GATA-3 can be positive in both PACC and urothelial carcinoma.5 Prostatic secretory cell markers PSA, PSAP and AMACR are usually negative or expressed in luminal cells in PACC.1-4 Neuroendocrine markers are negative and help to distinguish from neuroendocrine tumours such as small/large cell neuroendocrine carcinoma,5 particularly if PACC presents with large nests with necrosis. A subset of cases harbour the MYB::NFIB fusion (17-47%),6,7 as identified in adenoid cystic carcinoma in various anatomical sites, such as salivary glands8 and breast9. TMPRSS2-ERG rearrangement has not been identified in tested cases.10

PBCC are rare tumours. Of the cases described a significant proportion behaved in an indolent fashion. However, distant metastasis occurred in 14–29% of patients, half of whom died from the disease metastases.2,3

1. Amin MB, Berney DM, Compérat, EM, et al. Tumours of the prostate. In: WHO Classification of Tumours Editorial Board. Urinary and male genital tumours [Internet]. Lyon (France): International Agency for Research on Cancer; 2022 [cited 2022/3/8]. (WHO classification of tumours series, 5th ed.; vol. 8). Available from: https://tumourclassification.iarc.who.int/chapters/36.

2. Iczkowski KA, Ferguson KL, Grier DD, Hossain D, Banerjee SS, McNeal JE, Bostwick DG. Adenoid cystic/basal cell carcinoma of the prostate: clinicopathologic findings in 19 cases. Am J Surg Pathol. 2003 Dec; 27(12):1523-1529.

3. Ali TZ, Epstein JI. Basal cell carcinoma of the prostate: a clinicopathologic study of 29 cases. Am J Surg Pathol. 2007 May; 31(5):697-705.

4. Begnami MD, Quezado M, Pinto P, Linehan WM, Merino M. Adenoid cystic/basal cell carcinoma of the prostate: review and update. Arch Pathol Lab Med. 2007 Apr; 131(4):637-640.

5. He L, Metter C, Margulis V, Kapur P. A Review Leveraging a Rare and Unusual Case of Basal Cell Carcinoma of the Prostate. Case Rep Pathol. 2021 May 4; 2021:5520581.

6. Bishop JA, Yonescu R, Epstein JI, Westra WH. A subset of prostatic basal cell carcinomas harbor the MYB rearrangement of adenoid cystic carcinoma. Hum Pathol. 2015 Aug;46(8): 1204-1208.

7. Magers MJ, Iczkowski KA, Montironi R, Grignon DJ, Zhang S, Williamson SR, Yang X, Wang M, Osunkoya AO, Lopez-Beltran A, Hes O, Eble JN, Cheng L. MYB-NFIB gene fusion in prostatic basal cell carcinoma: clinicopathologic correlates and comparison with basal cell adenoma and florid basal cell hyperplasia. Mod Pathol. 2019 Nov;32(11) :1666-1674.

8. Brill LB 2nd, Kanner WA, Fehr A, Andrén Y, Moskaluk CA, Löning T, Stenman G, Frierson HF Jr. Analysis of MYB expression and MYB-NFIB gene fusions in adenoid cystic carcinoma and other salivary neoplasms. Mod Pathol. 2011 Sep; 24(9):1169-1176.

9. D’Alfonso TM, Mosquera JM, MacDonald TY, Padilla J, Liu YF, Rubin MA, Shin SJ. MYB-NFIB gene fusion in adenoid cystic carcinoma of the breast with special focus paid to the solid variant with basaloid features. Hum Pathol. 2014 Nov; 45(11):2270-2280.

10. Simper NB, Jones CL, MacLennan GT, Montironi R, Williamson SR, Osunkoya AO, Wang M, Zhang S, Grignon DJ, Eble JN, Tran T, Wang L, Baldrige LA, Cheng L. Basal cell carcinoma of the prostate is an aggressive tumor with frequent loss of PTEN expression and overexpression of EGFR. Hum Pathol. 2015 Jun;46(6): 805-812.

Laurence Galea(1), Scott Donnellan(2)

(1) Department of Anatomical Pathology, Melbourne Pathology (Sonic Healthcare), Victoria, Australia
(2) Department of Urology, Monash Health, Victoria, Australia

Prostate

Prostate, adenoid cystic carcinoma, basal cell carcinoma, basal cell hyperplasia, MYB.