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Mesonephric remnant hyperplasia: an unusual benign mimicker of prostate cancer
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Annals of Diagnostic Pathology 13 (2009) 402 – 404
Mesonephric remnant hyperplasia: an unusual benign mimicker of prostate cancer Mokrane Yacoub, MDa , Serge Milin, MDa , Jacques Irani, MD, PhDb , Gaëlle Fromont, MD, PhDa,⁎ a
Services d'Anatomie Pathologique, CHU Jean Bernard, Rue de la Miletrie, 86000 Poitiers, France b Service d'Urologie, CHU—Université de Poitiers, Poitiers, France
Abstract
Keywords:
Mesonephric remnant (MR) hyperplasia in the prostate is a rarely reported condition that is usually distinguished from prostatic adenocarcinoma by the absence of cytologic atypia as well as the absence of prostatic markers (prostate-specific antigen and prostatic acid phosphatase) expression. We report a case of prostatic MR hyperplasia with architectural and cytologic atypia in a 56-year-old man. The microscopic appearance strongly suggested malignancy, but immunohistochemistry allowed the diagnosis to be corrected. The presence of MRs in prostate tissues may be more common than appreciated or reported. Once the possibility is considered, the diagnosis is easily confirmed using immunochemistry. © 2009 Elsevier Inc. All rights reserved. Prostatic neoplasm; Mesonephric; Remnants
1. Introduction Mesonephric remnants (MR) are embryonic vestiges of the mesonephric ducts that can undergo hyperplasia [1], most often described in the female genital tract [2-4], where it can mimic adenocarcinoma. In males, only 15 cases of MR have been reported to 2003 (13 in the prostate, 1 in the prostatic urethra, and 1 in the seminal vesicle) [1]. The lesion was diagnosed in men aged 66 to 82 years, mostly in transurethral resection of prostate samples [1]. Mesonephric remnants in the prostate are composed of small glands lined by a single layer of cuboidal epithelial cells most often devoid of cytologic atypia. These cells have been shown to express the basal cell marker high molecular weight cytokeratin (HMWCK) 34βE12, without expression of the prostate lineage markers prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) [1-5]. Although this condition is considered benign, as in the female genital ⁎ Corresponding author. G. Fromont, MD, PhD, Service d’Anatomie Pathologique, CHU Jean Bernard, Rue de la Miletrie, 86000 Poitiers, France. Tel.: +33 0 5 49 44 40 23; fax: +33 0 5 49 44 39 47. E-mail address: [email protected] (G. Fromont). 1092-9134/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.anndiagpath.2009.03.008
tract, MR in the prostate can be mistaken for adenocarcinoma. However, its cytologic appearance usually allows separation from cancer. We describe herein a new case of prostatic MR hyperplasia with atypical histologic appearance. 2. Case report A 56-year-old man underwent transurethral resection (TUR) of prostate for symptoms of urinary obstruction. The preoperative PSA rate was 6 ng/mL. All the resected material (20 g) was totally embedded and examined. 2.1. Histology In addition to glandular and smooth muscle hyperplasia, microscopic examination showed on several samples numerous foci from 1 to 2 mm composed of atypical small glands infiltrating between the smooth muscle bundles and the prostatic gland. All foci had the same histologic features; the acini were typically small, round or oval, and lined by a single layer of low cuboidal cells with focal cytologic atypia and nucleoli. The lumen of the glands was devoid of eosinophilic secretion (Fig 1).
M. Yacoub et al. / Annals of Diagnostic Pathology 13 (2009) 402–404
403
Fig. 1. Focus of suspicious glands infiltrating between the smooth muscle bundles and the prostatic gland (A, hematoxylin-eosin-safran, original magnification ×40), atypical small acinar proliferation with atypia and nucleoli (B, hematoxylin-eosin-safran, original magnification ×400), confirmed as benign MRs after immunohistochemistry showing HMWCK positivity of basal cell layer of the normal gland and focal staining of the atypical small glands (C, original magnification ×200), diffuse p63 expression (D, original magnification ×200), and absence of p504S staining (E, original magnification ×200). The cells also diffusely expressed the AR (F, original magnification ×200).
2.2. Immunohistochemical study
3. Discussion
Immunohistochemistry was performed using the streptavidin–biotin method with the following primary antibodies directed against p63, α-methylacyl coenzyme A racemase (p504S), 34βE12, CD10, PSA, PAP, androgen receptor (AR), and Ki-67. The results are illustrated in Fig. 1. Surprisingly, the immunohistochemical study showed reactivity of the infiltrating acini with basal cell–associated markers, p63 and 34βE12, with a diffuse and focal staining, respectively. No positivity was found using both antibodies to prostate carcinoma–associated markers (p504S) and prostate lineage–specific markers PSA and PAP. All cells lining these atypical acini were positive for CD10 and AR. Only a few scattered cells were stained with the proliferation marker Ki-67.
This case illustrates an uncommon differential diagnosis consideration among small acinar proliferation in the prostate. The immunophenotype of the lesion led us to the diagnosis of MR, despite the presence of cytologic atypia. Only one previously reported case described occasional cytologic atypia in MR, which led the authors to the misdiagnosis of adenocarcinoma and radical prostatectomy [2]. In the present case, atypia and conspicuous nucleoli are more diffuse, but the lesion mimics infiltrative growth pattern without stromal reaction. Moreover, staining with Ki67 revealed only rare positive cells scattered, less than expected for a malignant lesion. In addition, no immunostaining was found for P504S, a useful tool to identify
404
M. Yacoub et al. / Annals of Diagnostic Pathology 13 (2009) 402–404
Table 1 Salient distinguishing features between mesonephric remnants hyperplasia (MRH) with and without atypia and malignant tumors mimickers
Acini size Cell layer Atypia HMWCK P63 P504S PSA AR CD10
AC/BCC [5,6]
Regular acinar carcinoma
P63 + adenocarcinoma [6]
MRH with atypia (our case)
MRH without atypia [1-7]
Large Several Yes + +/− NA − NA NA
Small 1 Yes − − + + + +/−
Small 1 Yes − + + + + NA
Small 1 Yes + + − − + +
Small 1 No + (6/8) NA NA − NA NA
AC/BCC indicates adenoid cystic/basal cell carcinoma; MRH, mesonephric remnants hyperplasia; NA, not available.
malignant lesion in the prostate, despite the fact that some “atrophic” cancers could be negative [3-5]. We observed that the cells lining the atypical small acini expressed not only the HMWCK 34βE12, as previously described in prostatic MR, but also p63. This finding, together with lack of PSA and PAP immunoreactivity, provided us with strong support for the diagnosis of MR. In fact, p63 is a basal cell marker absent in “regular” acinar prostatic carcinoma. p63 positivity can, however, be observed in adenoid cystic/basal cell carcinoma of the prostate [5,6], an exceptional type of prostatic cancer with histologic features different from small acinar proliferation, including the presence of several cell layers [3-5]. Aberrant diffuse expression of p63 has recently been reported in 21 otherwise typical small acinar prostate cancers [7]. p63 staining was associated with P504S expression and absence of HMWCK. In the present case, the positivity of HMWCK and absence of P504S staining ruled out the hypothesis of p63-positive small acinar prostate cancer. The fact that some prostate adenocarcinoma may express p63 also questioned upon the possible relationship between atypical MR hyperplasia and prostate cancer. Although affiliation between MR hyperplasia and mesonephric adenocarcinoma has been reported in the female genital tract [2-4], such relation ship has never been described in the prostate. Both CD10 and AR expression have previously been observed in tissues of mesonephric origin [2]. The presence of AR in prostatic MR could allow a hormonal related growth, leading to hyperplasia of the remnants. The
differential diagnosis of MR on prostate transurethral resection, focused on malignant conditions, are summarized in Table 1. It is likely that MR hyperplasia might be an underrecognized condition on prostate samples. Typical MR hyperplasia might be interpreted as other benign small glandular lesions, with no clinical consequences. In contrast, atypical MR hyperplasia, as in our case, may be misdiagnosed as prostate cancer. Pathologists must, therefore, be aware of this entity because the diagnosis can be easily confirmed by immunohistochemistry. References [1] Bostwick DG, Qian J, Ma J, Muire TE. Mesonephric remnants of the prostate: incidence and histologic spectrum. Mod Pathol 2003;16:630-5. [2] Gikas PW, Del Buono EA, Epstein JI. Florid hyperplasia of mesonephric remnants involving prostate and periprostatic tissue. Am J Surg Pathol 1993;17:454-60. [3] Srigley JR. Benign mimickers of prostatic adenocarcinoma. Mod Pathol 2004;17:328-48. [4] McGluggage WG, Ganesan R, Hirschowitz L, Miller K, Rollason TP. Ectopic prostatic tissue in the uterine cervix and vagina : report of a series with a detailed immunohistochemical analysis. Am J Surg Pathol 2006;30:209-15. [5] Paner GP, Luthringer DJ, Amin MB. Best practice in diagnostic immunohistochemistry prostate carcinoma and its mimics in needle core biopsies. Arch Pathol Lab Med 2008;132:1388-96. [6] Iczkowski KA, Ferguson KL, Grier DD, Hossain D, Banerjee SS, McNeal JE, et al. Adenoid cystic/basal cell carcinoma of the prostate: clinicopathologic findings in 19 cases. Am J Surg Pathol 2003;27:1523-9. [7] Osunkoya AO, Hansel DE, Sun X, Netto GJ, Epstein JI. Aberrant diffuse expression of p63 in adenocarcinoma of the prostate on needle biopsy and radical prostatectomy: report of 21 cases. Am J Surg Pathol 2008;32:461-7.
Annals of Diagnostic Pathology 13 (2009) 402 – 404
Mesonephric remnant hyperplasia: an unusual benign mimicker of prostate cancer Mokrane Yacoub, MDa , Serge Milin, MDa , Jacques Irani, MD, PhDb , Gaëlle Fromont, MD, PhDa,⁎ a
Services d'Anatomie Pathologique, CHU Jean Bernard, Rue de la Miletrie, 86000 Poitiers, France b Service d'Urologie, CHU—Université de Poitiers, Poitiers, France
Abstract
Keywords:
Mesonephric remnant (MR) hyperplasia in the prostate is a rarely reported condition that is usually distinguished from prostatic adenocarcinoma by the absence of cytologic atypia as well as the absence of prostatic markers (prostate-specific antigen and prostatic acid phosphatase) expression. We report a case of prostatic MR hyperplasia with architectural and cytologic atypia in a 56-year-old man. The microscopic appearance strongly suggested malignancy, but immunohistochemistry allowed the diagnosis to be corrected. The presence of MRs in prostate tissues may be more common than appreciated or reported. Once the possibility is considered, the diagnosis is easily confirmed using immunochemistry. © 2009 Elsevier Inc. All rights reserved. Prostatic neoplasm; Mesonephric; Remnants
1. Introduction Mesonephric remnants (MR) are embryonic vestiges of the mesonephric ducts that can undergo hyperplasia [1], most often described in the female genital tract [2-4], where it can mimic adenocarcinoma. In males, only 15 cases of MR have been reported to 2003 (13 in the prostate, 1 in the prostatic urethra, and 1 in the seminal vesicle) [1]. The lesion was diagnosed in men aged 66 to 82 years, mostly in transurethral resection of prostate samples [1]. Mesonephric remnants in the prostate are composed of small glands lined by a single layer of cuboidal epithelial cells most often devoid of cytologic atypia. These cells have been shown to express the basal cell marker high molecular weight cytokeratin (HMWCK) 34βE12, without expression of the prostate lineage markers prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) [1-5]. Although this condition is considered benign, as in the female genital ⁎ Corresponding author. G. Fromont, MD, PhD, Service d’Anatomie Pathologique, CHU Jean Bernard, Rue de la Miletrie, 86000 Poitiers, France. Tel.: +33 0 5 49 44 40 23; fax: +33 0 5 49 44 39 47. E-mail address: [email protected] (G. Fromont). 1092-9134/$ – see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1016/j.anndiagpath.2009.03.008
tract, MR in the prostate can be mistaken for adenocarcinoma. However, its cytologic appearance usually allows separation from cancer. We describe herein a new case of prostatic MR hyperplasia with atypical histologic appearance. 2. Case report A 56-year-old man underwent transurethral resection (TUR) of prostate for symptoms of urinary obstruction. The preoperative PSA rate was 6 ng/mL. All the resected material (20 g) was totally embedded and examined. 2.1. Histology In addition to glandular and smooth muscle hyperplasia, microscopic examination showed on several samples numerous foci from 1 to 2 mm composed of atypical small glands infiltrating between the smooth muscle bundles and the prostatic gland. All foci had the same histologic features; the acini were typically small, round or oval, and lined by a single layer of low cuboidal cells with focal cytologic atypia and nucleoli. The lumen of the glands was devoid of eosinophilic secretion (Fig 1).
M. Yacoub et al. / Annals of Diagnostic Pathology 13 (2009) 402–404
403
Fig. 1. Focus of suspicious glands infiltrating between the smooth muscle bundles and the prostatic gland (A, hematoxylin-eosin-safran, original magnification ×40), atypical small acinar proliferation with atypia and nucleoli (B, hematoxylin-eosin-safran, original magnification ×400), confirmed as benign MRs after immunohistochemistry showing HMWCK positivity of basal cell layer of the normal gland and focal staining of the atypical small glands (C, original magnification ×200), diffuse p63 expression (D, original magnification ×200), and absence of p504S staining (E, original magnification ×200). The cells also diffusely expressed the AR (F, original magnification ×200).
2.2. Immunohistochemical study
3. Discussion
Immunohistochemistry was performed using the streptavidin–biotin method with the following primary antibodies directed against p63, α-methylacyl coenzyme A racemase (p504S), 34βE12, CD10, PSA, PAP, androgen receptor (AR), and Ki-67. The results are illustrated in Fig. 1. Surprisingly, the immunohistochemical study showed reactivity of the infiltrating acini with basal cell–associated markers, p63 and 34βE12, with a diffuse and focal staining, respectively. No positivity was found using both antibodies to prostate carcinoma–associated markers (p504S) and prostate lineage–specific markers PSA and PAP. All cells lining these atypical acini were positive for CD10 and AR. Only a few scattered cells were stained with the proliferation marker Ki-67.
This case illustrates an uncommon differential diagnosis consideration among small acinar proliferation in the prostate. The immunophenotype of the lesion led us to the diagnosis of MR, despite the presence of cytologic atypia. Only one previously reported case described occasional cytologic atypia in MR, which led the authors to the misdiagnosis of adenocarcinoma and radical prostatectomy [2]. In the present case, atypia and conspicuous nucleoli are more diffuse, but the lesion mimics infiltrative growth pattern without stromal reaction. Moreover, staining with Ki67 revealed only rare positive cells scattered, less than expected for a malignant lesion. In addition, no immunostaining was found for P504S, a useful tool to identify
404
M. Yacoub et al. / Annals of Diagnostic Pathology 13 (2009) 402–404
Table 1 Salient distinguishing features between mesonephric remnants hyperplasia (MRH) with and without atypia and malignant tumors mimickers
Acini size Cell layer Atypia HMWCK P63 P504S PSA AR CD10
AC/BCC [5,6]
Regular acinar carcinoma
P63 + adenocarcinoma [6]
MRH with atypia (our case)
MRH without atypia [1-7]
Large Several Yes + +/− NA − NA NA
Small 1 Yes − − + + + +/−
Small 1 Yes − + + + + NA
Small 1 Yes + + − − + +
Small 1 No + (6/8) NA NA − NA NA
AC/BCC indicates adenoid cystic/basal cell carcinoma; MRH, mesonephric remnants hyperplasia; NA, not available.
malignant lesion in the prostate, despite the fact that some “atrophic” cancers could be negative [3-5]. We observed that the cells lining the atypical small acini expressed not only the HMWCK 34βE12, as previously described in prostatic MR, but also p63. This finding, together with lack of PSA and PAP immunoreactivity, provided us with strong support for the diagnosis of MR. In fact, p63 is a basal cell marker absent in “regular” acinar prostatic carcinoma. p63 positivity can, however, be observed in adenoid cystic/basal cell carcinoma of the prostate [5,6], an exceptional type of prostatic cancer with histologic features different from small acinar proliferation, including the presence of several cell layers [3-5]. Aberrant diffuse expression of p63 has recently been reported in 21 otherwise typical small acinar prostate cancers [7]. p63 staining was associated with P504S expression and absence of HMWCK. In the present case, the positivity of HMWCK and absence of P504S staining ruled out the hypothesis of p63-positive small acinar prostate cancer. The fact that some prostate adenocarcinoma may express p63 also questioned upon the possible relationship between atypical MR hyperplasia and prostate cancer. Although affiliation between MR hyperplasia and mesonephric adenocarcinoma has been reported in the female genital tract [2-4], such relation ship has never been described in the prostate. Both CD10 and AR expression have previously been observed in tissues of mesonephric origin [2]. The presence of AR in prostatic MR could allow a hormonal related growth, leading to hyperplasia of the remnants. The
differential diagnosis of MR on prostate transurethral resection, focused on malignant conditions, are summarized in Table 1. It is likely that MR hyperplasia might be an underrecognized condition on prostate samples. Typical MR hyperplasia might be interpreted as other benign small glandular lesions, with no clinical consequences. In contrast, atypical MR hyperplasia, as in our case, may be misdiagnosed as prostate cancer. Pathologists must, therefore, be aware of this entity because the diagnosis can be easily confirmed by immunohistochemistry. References [1] Bostwick DG, Qian J, Ma J, Muire TE. Mesonephric remnants of the prostate: incidence and histologic spectrum. Mod Pathol 2003;16:630-5. [2] Gikas PW, Del Buono EA, Epstein JI. Florid hyperplasia of mesonephric remnants involving prostate and periprostatic tissue. Am J Surg Pathol 1993;17:454-60. [3] Srigley JR. Benign mimickers of prostatic adenocarcinoma. Mod Pathol 2004;17:328-48. [4] McGluggage WG, Ganesan R, Hirschowitz L, Miller K, Rollason TP. Ectopic prostatic tissue in the uterine cervix and vagina : report of a series with a detailed immunohistochemical analysis. Am J Surg Pathol 2006;30:209-15. [5] Paner GP, Luthringer DJ, Amin MB. Best practice in diagnostic immunohistochemistry prostate carcinoma and its mimics in needle core biopsies. Arch Pathol Lab Med 2008;132:1388-96. [6] Iczkowski KA, Ferguson KL, Grier DD, Hossain D, Banerjee SS, McNeal JE, et al. Adenoid cystic/basal cell carcinoma of the prostate: clinicopathologic findings in 19 cases. Am J Surg Pathol 2003;27:1523-9. [7] Osunkoya AO, Hansel DE, Sun X, Netto GJ, Epstein JI. Aberrant diffuse expression of p63 in adenocarcinoma of the prostate on needle biopsy and radical prostatectomy: report of 21 cases. Am J Surg Pathol 2008;32:461-7.