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Keywords:

  • basal cell carcinoma;
  • immunohistochemistry;
  • prostate

Abstract

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case report
  5. Discussion
  6. References

Abstract:  Prostatic basal cell carcinoma (BCC), a distinctive variant of adenocarcinoma, is rare. We report a patient with pure basaloid BCC showing an extraprostatic extension and lymph node metastases. A 67-year-old man with urinary outlet obstruction was referred to our hospital. Digital rectal examination disclosed a stony hard prostate. Serum prostate-specific antigen and prostatic acid phosphatase were within the normal range. Transrectal needle biopsy of the prostate was followed by transurethral resection as symptomatic treatment. The lesion was diagnosed histopathologically as BCC. Despite antiandrogen therapy distant metastases developed, and the patient died 5 months postoperatively. We discuss the histological and immunohistochemical findings in this case.


Introduction

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case report
  5. Discussion
  6. References

Prostate gland epithelium is composed of secretory and basal cells. Basal cells may act as stem cells in the prostate gland, with the potential to differentiate along divergent pathways. These cells might also maintain the secretory cells under hormonal regulation.1 Lesions of basal cells in the prostate gland span a wide range from benign basal cell hyperplasia through varying ranges of atypia to basal cell carcinoma (BCC) which includes types termed prostatic basaloid carcinoma and adenoid cystic carcinoma (ACC).2 Although prostatic basal cell hyperplasia is a common feature of nodular hyperplasia, BCC is extremely rare. We report a patient with prostatic BCC and review similar previously reported cases.

Case report

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case report
  5. Discussion
  6. References

A 67-year-old Japanese man with frequent and difficult urination was admitted to our hospital in April 2006. Digital rectal examination disclosed slight prostatic enlargement and a stony hard consistency. Serum prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) concentrations were within normal range (0.08 ng/mL and 1.1 ng/mL, respectively). Histological examination of a prostatic transrectal needle biopsy specimen suggested either an atypical prostatic carcinoma or invasion of the prostate by a high-grade urothelial carcinoma.

Magnetic resonance imaging (MRI) depicted the prostate as enlarged and replaced by a tumor that directly invaded the seminal vesicle and bladder wall (Fig. 1). Left internal iliac and para-aortic lymph nodes were enlarged, implying tumor metastases. On cystoscopic examination, the surface of the bladder mucosa was normal. A clinical tumor-nodes-metastasis (TNM) stage of T4N1M1a was assigned.

image

Figure 1. T2-weighted magnetic resonance imaging of the pelvis revealed a large, irregular tumor mass (arrow).

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Palliative transurethral resection of the prostate (TUR-P) was performed on 13 July to relieve obstructive symptoms and provide tissue for definitive histological diagnosis. Five grams of prostatic tissue were resected, after which normal voiding was restored. Pathological evaluation established a diagnosis of basal cell carcinoma. Hormonal therapy was initiated with a luteinizing hormone releasing hormone (LH-RH) agonist, leuprorelin acetate (Leuplin), and an antiandrogen agent, bicalutamide (Casodex). However, a right inguinal lymph node metastasis was documented in September 2006. The patient refused any intervention due to liver dysfunction and his condition rapidly deteriorated. He died on 15 December, 8 months following presentation to our hospital.

Biopsy and resection specimens from the prostate were fixed in 10% buffered formalin and embedded in paraffin. Sections cut at a 4-μm thickness were stained with hematoxylin and eosin or processed immunohistochemically using a commercially available kit (EnVision Plus-HRP; Dako).

Histologically, the tumor was composed of solid nests of small, round cells with scant cytoplasm, arrayed in a basaloid growth pattern. The tumor showed extensive vascular and perineural invasion. Transition from the normal epithelium to tumor cells within a single prostatic gland was seen. The tumor cells were consistently immunoreactive for p63, high-molecular-weight cytokeratins (34βE12 and CK5/6), and androgen receptor (AR). PAP staining was focal and weak. No staining was seen for PSA, chromogranin A, or cytokeratins 7 and 20 (Fig. 2; Table 1).

image

Figure 2. Histological and immunohistochemical findings in the prostate tumor (a–c). The tumor cells proliferate in a solid nest pattern, and present round nuclei and scant cytoplasm (a). Tumor cells are immunoreactive for 34βE12 showing transitional areas between tumor tissue and normal glands (arrows) (b). The fraction of Ki-67-positive cells among tumor cells is approximately 70% (c). Objective magnifications: ×20 in a; ×4 in b; ×10 in c.

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Table 1.  Results of immunohistochemical staining
  1. AR, androgen receptor; CEA, carcinoembryonic antigen; CK, cytokeratin; ER, estrogen receptor; PAP, prostatic acid phosphatase; PgR, progesterone receptor; PSA, prostate-specific antigen; SMA, smooth muscle actin.

AE1/AE3 (+)PSA (–)
34βE12 (+)PAP (weakly +)
CK5/6 (+)P504S (–)
p63 (+)D2-40 (–)
CK7 (–)Chromogranin A (–)
CK20 (–)bcl-2 (focally +)
AR (+)c-erbB-2 oncoprotein (+)
ER/PgR (–)/(–)p53 (+)
SMA (–)
S-100 protein (–)Ki-67 index ≈70%
CEA (–)

Discussion

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case report
  5. Discussion
  6. References

The great majority of prostatic carcinomas arise from secretory epithelium of glands, and are associated with elevated serum PSA. Normal serum PSA and the absence of immunohistochemical staining for PSA in the present case suggest that the tumor originated from a cell different from the secretory epithelial cell.3 The differential diagnosis included poorly differentiated adenocarcinoma, BCC, and urothelial carcinoma invading the prostate.4 Poorly differentiated adenocarcinoma may be non-reactive for PSA, but the presence of immunoreactivity for both p63 and high-molecular-weight cytokeratin were helpful in excluding conventional adenocarcinoma. On the other hand, urothelial carcinomas typically express cytokeratins 7 and 20 in addition to p63 and high-molecular-weight cytokeratin.5 Immunoreactivity of the present tumor for 34βE12, CK5/6, and p63, coupled with the absence of immunoreactivity for cytokeratins 7 and 20, strongly favored a diagnosis of BCC.4,6 Staining for C-erbB-2 oncoprotein and p53, as well as high mitotic activity, indicated that this tumor was highly malignant. According to morphological patterns, BCC has been divided into two histological types: adenoid cystic and basaloid. The present tumor represented the basaloid type.

Additional histological features that indicate malignant potential in these tumors include invasive growth patterns, such as extensive infiltration among benign prostatic glandular elements, perineural invasion, and extraprostatic extension; the presence of necrosis; high proliferative activity; and the presence of metastases.7

Our patient's tumor was clinically malignant: the invasion extending beyond the prostatic capsule and lymph node metastases were obvious. Along with findings using hematoxylin and eosin, an elevated Ki-67 labeling index can help to establish the diagnosis of basaloid carcinoma of the prostate, as Ki-67 can allow distinction between benign and malignant prostatic basal cell lesions.8 In this case the labeling index for Ki-67 was high reaching 70%. Expression of Ki-67 in conventional adenocarcinomas can have a wide range, but is much lower (typical labeling index, 0.4% to 9.1%).9

Clinicopathological data for the present case of basaloid type BCC and four previously reported cases are summarized in Table 2. Considering the limited clinical outcome data available, these tumors have been viewed as having ‘low malignant potential’.2 Most of the few reported cases were locally aggressive lesions without distant metastases, and radical surgery or radiotherapy were performed. Follow-up periods most often were relatively short. In BCC with both adenoid cystic and basaloid features, those with a prominent basaloid pattern were more aggressive.4 Our case, a pure basaloid-type BCC, underscores a clinically more aggressive nature than that shown by the adenoid cystic type. In actuality, neither biological behavior nor optimal treatment of BCC are well defined in view of the limited case material with relatively short follow-up periods.

Table 2.  Basaloid-type basal cell carcinomas of the prostate
Author AgeSymptomMetastasisTreatmentFollow-up
  1. CT, chemotherapy; DOD, dead of disease; HT, hormonal therapy; N/A, not available; NED, no evidence of disease; RP, radical prostatectomy; RT, radiation therapy; TURP, transurethral resection of prostate.

Denholm et al.3199228N/A(–)TURP + RT/CTNED, 18 m
Iczkowski et al.6200363Obstruction(–)TURP, RPNED, 5.6 years
Iczkowski et al.6200381Obstruction(–)TURPNED, 3 m
McKenney et al.10200453N/A(–)RP + RTNED, 3 years
This case200767Frequency Obstruction(+)TURP, HTDOD, 5 m

No reported case included conclusive evidence of distant metastases except for the present one.

As our patient's tumor was positive for AR, androgen-deprivation therapy was attempted, but without success.

As explained above, little generalization can be made about the prognosis or mode of behavior of BCC, nor about the most appropriate choice of treatment. There is no consensus on the management of BCC about chemotherapy. BCC is rare among tumors arising from the prostate, but this case should highlight the grave implications of the basaloid type.

In conclusion, our case shows that BCC with only basaloid features is likely to be aggressive and resistant to hormonal therapy. Correct identification is essential for adequate clinical staging and for planning the treatment of this disease.

References

  1. Top of page
  2. Abstract
  3. Introduction
  4. Case report
  5. Discussion
  6. References