SEARCH

SEARCH BY CITATION

Keywords:

  • amyloid;
  • prostate;
  • prostate-specific antigen;
  • seminal vesicles.

Abstract

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

Abstract  Transrectal ultrasound-guided biopsy of the prostate is an integral step in the investigation of patients at risk of prostate adenocarcinoma. With an increasing number of biopsies being performed, uncommon forms of prostatic pathology will be identified more frequently. Amyloidosis of the prostate and/or the seminal vesicles may be noted on transrectal ultrasound-guided biopsy of the prostate and the implications of this histological diagnosis must be understood. We present our experience of two such cases of amyloidosis and review the literature regarding their management.


Introduction

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

Amyloidosis of the prostate is a rare disease. With more patients undergoing transrectal ultrasound (TRUS) guided biopsy of the prostate to exclude malignancy, the likelihood of identifying primary or secondary amyloidosis increases. The initial indication for prostatic biopsy is often based on an unexplained raised serum prostate-specific antigen (PSA) level, with or without suspicious digital rectal examination findings. The place of TRUS biopsy diagnosed amyloidosis in accounting for an elevated serum PSA level has not previously been reviewed.

Amyloidosis is a disease characterized by tissue deposition of rigid, non-branching fibrils having a twisted β-pleated sheet confirmation. Fibrils may be derived from various proteins by differing pathological mechanisms.1 Amyloidosis may be systemic or localized.

We report on two cases of amyloidosis found on TRUS-guided prostatic biopsy and review the relevant literature.

Case reports

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

Case 1

A 70-year-old gentleman presented for assessment of moderate obstructive voiding symptoms. He had a known history of systemic amyloidosis (untreated) and the rest of his history was otherwise unremarkable. Examination per rectum revealed a nodular, firm prostate, suspicious for carcinoma. His PSA level was raised at 7.1 µg/L (normal, <4.0 µg/L) and a TRUS-guided biopsy was performed. The ultrasound findings were of normal echogenicity throughout and histology revealed mild benign adenomatous hyperplasia and primary amyloidosis of the prostate in all cores, but no evidence of malignancy. The histological diagnosis of primary amyloidosis was supported by the widespread deposition of amyloid in the stroma and walls of blood vessels and was consistent with the past history of the patient (Fig. 1a). The amyloid was resistant to pretreatment with potassium permanganate prior to staining with Congo red, confirming primary amyloid deposits (Fig. 1b). The patient had a repeat PSA test 3 months later that was essentially unchanged and he will be carefully monitored into the future with repeat PSA level tests.

image

Figure 1. Histology of case 1 with a single prostatic biopsy core demonstrating widespread deposition of amyloid in the stroma and walls of blood vessels with hematoxylin and eosin stain (a) and staining brightly with Congo red (b), due to resistance of the amyloid to pretreatment with potassium permanganate, consistent with primary amyloidosis.

Download figure to PowerPoint

Case 2

A 73-year-old man presented as a referral from his family practitioner with a nodule noted on his annual rectal examination and a mildly raised PSA level of 5.2 µg/L. He had only minor obstructive voiding symptoms and the rest of his history was unremarkable. After consultation and examination confirming the prostatic nodule, he elected to undergo TRUS, which was normal despite the nodule and biopsies, to exclude malignancy. Again, no malignancy was detected, only mild adenomatous changes. Two cores also included portions of the seminal vesicles which had stroma separated by widespread deposition of amyloid (amorphous eosinophilic material; Fig. 2a). Congo red stain was again positive and there was apple green birefringence under polarized light (Fig. 2b). However, there was a loss of affinity to Congo red following pretreatment with potassium permanganate consistent with secondary amyloid deposition. His PSA level remains steady and he will undergo biopsy again only if a significant rise is detected in the future.

image

Figure 2. Histology of case 2 with the seminal vesicle biopsy demonstrating widespread deposition of amyloid (amorphous eosinophilic material) with hematoxylin and eosin stain (a) and loss of affinity of the amyloid to Congo red (b) after pretreatment with potassium permanganate prior to staining, consistent with secondary amyloidosis.

Download figure to PowerPoint

Discussion

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

Amyloidosis may be divided into systemic and localized forms. Systemic forms are subdivided based on the type of rigid non-branching fibrils that are deposited. Primary (idiopathic or associated with multiple myeloma) amyloidosis consists of monoclonal antibody light (AL) chain deposits, whilst secondary amyloidosis is associated with chronic inflammation and consists of amyloid A protein (AA). Other hereditary and senile forms have been described.2 Localized or organ-limited amyloidoses mainly affects the brain, heart or pancreas, with the genitourinary tract being a rare location.1

Clinical manifestations of amyloidosis are varied and depend entirely on the biochemical nature of the fibril protein and the area of the body that is involved.3 Usually, amyloidosis is a slowly progressive disease that is frequently seen as a concomitant of aging.1 Treatment usually is directed towards reducing precursor production, inhibiting the synthesis and extracellular deposition of amyloid fibrils and promoting lysis of existing amyloid deposits.2 Often, a poor response ensues, even with aggressive treatment.

In 1973, Wilson et al. studied prostatic material and found amyloid depositions in 10% (8/75) of a random population and in 47% (8/17) of a selected population (primary amyloidosis, multiple myeloma and paraplegia).4 Interestingly, Lupovitch studied open prostatectomy specimens and found amyloidosis in only 1.5% of patients (4/262).5 Only five other case reports of amyloidosis of the prostate, both systemic and localized in nature, have been recorded in the literature to date.2,3,6,7 Amyloidosis may change the texture of the prostate gland due to its associated inflammatory response, as occurred in both cases above. No specific findings on ultrasound, such as altered echogenicity have been reported, as seen in both of the present cases. The association of amyloidosis with prostatic adenocarcinoma has been reported at between 2% and 25%.4,5 Aging has been noted as a risk factor for prostatic amyloidosis5 and this also may explain the association with prostatic adenocarcinoma.

The ability to differentiate primary and secondary amyloids by immunohistochemistry was described by Wright et al. in 1977.8 All types of amyloid have an affinity for Congo red staining because their amyloid protein fibrils have an antiparallel α-pleated sheet conformation. However, when pretreated with potassium permanganate prior to staining, secondary amyloid deposits (AA) demonstrate a loss of affinity to Congo red (Fig. 2b). This is because potassium permanganate denatures the amyloid protein (AA) by altering the α-pleated sheet conformation. Primary amyloid deposits (AL) stain brightly with Congo red even after pretreatment with potassium permanganate (Fig. 1b), because they can resist denaturation.

Corpora amylacea are reported present in up to 80% of examined prostate glands5 and often stain positive for amyloid. However, these deposits are unrelated to systemic or other localized amyloidosis of the prostate.4,9

Seminal vesicle involvement was reported more often than prostatic involvement across 90 cases cited by Seidman et al. in a review in 1989, with a further 20 cases reported since.1,9,10 In the majority of reported cases, there is no indication of systemic amyloidosis. Prior to this report, only two other cases of systemic amyloidosis affecting the seminal vesicles have been reported.1

Neither localized prostate nor seminal vesicle involvement alone requires treatment. However, treatment may be warranted if systemic amyloidosis is affecting multiple organs.

Amyloidosis is likely to increase serum PSA by virtue of associated inflammation, in the manner noted with multiple other causes of prostatic inflammation. However, the raised serum PSA levels noted in these instances may be due, in part, to coincident benign adenomatous hyperplasia. In both of the presented cases, we elected to manage expectantly with serial serum PSA levels and to re-biopsy as clinically indicated.

Other organs should be biopsied to exclude the presence of amyloidosis if clinically indicated. An elevated serum PSA should not be assumed to be due to amyloidosis alone and clinicians should be satisfied they have excluded malignancy before reassuring patients with known amyloidosis. Seminal vesicle involvement is more common than prostatic involvement and appears to be associated with aging.

References

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