Prostate gland & seminal vesicles

Nonneoplastic

Nonneoplastic metaplasia


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Deputy Editor-in-Chief: Maria Tretiakova, M.D., Ph.D.
Kenneth A. Iczkowski, M.D.

Last author update: 19 March 2024
Last staff update: 19 March 2024

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PubMed Search: Nonneoplastic metaplasia

Kenneth A. Iczkowski, M.D.
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Cite this page: Iczkowski KA. Nonneoplastic metaplasia. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/prostatenonneoplasticmet.html. Accessed June 16th, 2024.
Mucinous metaplasia
Definition / general
  • Mucinous metaplasia is a form of glandular differentiation

Essential features
  • Acini with tall, mucin filled cells with flat, basal pyknotic nuclei
  • May occur as a group of glands or single cells within glands
  • More common in the periurethral area
  • May mimic cancer but not associated with malignancy
  • Resembles Cowper glands

Epidemiology

Sites
  • Prostate

Pathophysiology
  • Pathophysiology and etiology are unknown

Etiology

Clinical features
  • The only clinical significance is that it may mimic cancer in a needle biopsy

Diagnosis
  • Mucin filled vacuoles distend the cytoplasm of benign cells

Treatment
  • Not required
  • Mucinous metaplasia is a morphologic variant of prostatic acini

Microscopic (histologic) description
  • Acini with tall mucin filled cells with flat, basal pyknotic nuclei

Microscopic (histologic) images

Contributed by Kenneth A. Iczkowski, M.D.
Focal mucinous metaplasia

Focal mucinous metaplasia

Reactive change and mucinous metaplasia

Reactive change and mucinous metaplasia



Positive stains

Negative stains

Differential diagnosis

Additional references
Paneth cell-like change
Definition / general

Essential features
  • Small focus of cells with bright pink granules in cytoplasm
  • No cytologic atypia

Terminology

Epidemiology

Pathophysiology
  • It is a reactive change of the prostatic epithelium, often seen with inflammation

Etiology

Clinical features
  • Hormone therapy, radiotherapy, inflammation

Diagnosis
  • Morphology

Laboratory
  • Serum prostate specific antigen (PSA) is elevated if associated with inflammation or benign prostatic hyperplasia (BPH)

Case reports
  • 49 and 52 year old men with serum PSAs of 4 - 5 ng/mL and incidental findings in benign biopsies (Int J Clin Exp Pathol 2014;7:3454)
  • 68 year old man with nonspecific granulomatous prostatitis in association with eosinophilic epithelial metaplasia and prostatic adenocarcinoma (Indian J Pathol Microbiol 2017;60:409)
  • 71 year old man with serum PSA of 10 ng/mL in association with nonspecific granulomatous prostatitis and BPH (APMIS 2005;113:564)

Treatment
  • Not required

Microscopic (histologic) description
  • Nests of squamous epithelial cells with eosinophilic cytoplasm and focal keratin
  • Mitoses may be seen but should not be frequent

Microscopic (histologic) images

Contributed by Kenneth A. Iczkowski, M.D.
Paneth cell metaplasia, bottom

Paneth cell metaplasia, bottom

P504S reactivity

P504S reactivity

PAS positive, diastase resistant

PAS positive, diastase resistant



Positive stains

Negative stains

Electron microscopy description

Differential diagnosis
  • Possible differential diagnosis is prostatic adenocarcinoma with Paneth cell differentiation:
    • Those lesions have infiltrating, angulated glands, often with collapsed gland lumina, although they tend to be of low grade and low stage (Hum Pathol 2020;102:7)
    • In contrast, benign Paneth cell metaplasia has well rounded, uniform and circumscribed groups of glands without atypia
  • Cancer of no specific type:
    • Also has strong P504S reactivity but would have atypia and lack a granular pink cytoplasm
Squamous metaplasia
Definition / general
  • Squamous metaplasia is usually an incidental finding in the setting of infarction in the nodules of benign prostatic hyperplasia (BPH) or secondary to treatment (hormonal therapy and radiation)

Essential features
  • Usually an incidental finding in the setting of inflammation, acute infarction of benign prostatic hyperplasia or secondary to hormone / radiation therapy or following prostatic artery embolization therapy for benign prostatic hyperplasia
  • Can present with cytologic atypia that is reactive to the underlying process
  • Key to avoiding misinterpretation as cancer is to identify the underlying cause (i.e., adjacent hemorrhage or obvious necrosis indicating infarction, clinical history of hormone therapy or radiation)

Epidemiology
  • ~0.3% incidence in unselected series (Urol J 2009;6:109)
  • Seen in transurethral resection of the prostate (TURP) specimens, some with benign prostatic hyperplasia, particularly with infarct of nodules of BPH; also associated with radiation
  • Feminizing hormone therapy for gender transition (Arch Pathol Lab Med 2022;146:252)

Pathophysiology
  • It is a reactive change of the prostatic epithelium

Etiology

Diagnosis
  • Cells are nonneoplastic without atypia
    • They should have a pavemented configuration with crisp cell borders, intracellular keratin, extracellular keratin pearls or intercellular bridges (tonofilaments) visible on high power

Treatment
  • Not required

Microscopic (histologic) description
  • Nests of squamous epithelial cells with eosinophilic cytoplasm and focal keratinization
  • Mitoses can be seen but should not be frequent

Microscopic (histologic) images

Contributed by Kenneth A. Iczkowski, M.D.
Keratinizing squamous metaplasia

Keratinizing squamous metaplasia

Posttherapeutic squamous metaplasia

Posttherapeutic squamous metaplasia

Benign squamous metaplasia and cancer

Benign squamous metaplasia and cancer

Focal squamous metaplasia

Focal squamous metaplasia



Positive stains
  • Squamous metaplasia is positive for the classic squamous markers, including p63, CK5/6, HMWCK

Negative stains

Differential diagnosis
  • Main differential diagnoses are squamous cell carcinoma and urothelial carcinoma
  • Differential diagnosis is based on the degree of cytologic atypia and the presence of stromal invasion
    • Squamous cell carcinoma has intercellular bridges and intracellular or extracellular keratin while urothelial carcinoma does not

Additional references
Urothelial metaplasia
Definition / general
  • Urothelium normally lines the glands and ducts of the prostate

Essential features
  • Epithelium contains oval or spindle cells with occasional nuclear grooves
  • Urothelial cells may be located underneath the prostatic luminal epithelium
  • Prostatic ducts may also show the spread of urothelial carcinoma but in contrast to urothelial metaplasia, carcinoma has high grade nuclear atypia, similar to carcinoma in situ in the bladder

Epidemiology
  • Urothelial metaplasia is an exceedingly common finding, at any age

Sites
  • Peripheral prostate acini and ducts

Clinical features
  • Urothelial metaplasia is a histologic finding and has no clinical manifestations

Diagnosis
  • Diagnosis of urothelial metaplasia is morphologic

Treatment
  • Not required

Gross description
  • Urothelial metaplasia is not seen grossly

Microscopic (histologic) description
  • Epithelium is multilayered, with oval or spindle cells with occasional nuclear grooves (Ann Diagn Pathol 2019;38:11)
  • Focally, the cells may be oriented parallel to the basement membrane
  • Urothelial cells may be located underneath a prostatic luminal epithelium

Microscopic (histologic) images

Contributed by Andres Matoso, M.D., Ziad El-Zaatari, M.D. and Kenneth A. Iczkowski, M.D.
Group of prostatic ducts

Group of prostatic ducts

Urothelial metaplasia, prostatic ducts Urothelial metaplasia, prostatic ducts Urothelial metaplasia, prostatic ducts

Urothelial metaplasia, prostatic ducts

Urothelial metaplasia

Urothelial metaplasia



Positive stains
  • Stains positive for urothelial markers include p63, GATA3

Negative stains

Differential diagnosis
  • Urothelial carcinoma spreading in prostatic ducts:
    • In contrast to urothelial metaplasia, urothelial carcinoma is characterized by high grade nuclear atypia
  • Intraductal prostatic adenocarcinoma:
    • This is another multilayered epithelium but it would be solid to cribriform growth, with marked nuclear enlargement and prominent nucleoli, surrounded by basal cells
  • High grade prostatic intraepithelial neoplasia:
    • Multilayering of epithelium but usually with a tufted or micropapillary pattern
    • Atypia is present but to a lesser degree than in intraductal prostatic carcinoma
  • Urothelial metaplasia has been reported in the seminal vesicle (Ann Diagn Pathol 2012;16:145)
    • In that location, golden-brown pigmented granules and a widely branched pattern of epithelium would be distinctive
Board review style question #1

Which type of benign metaplasia in the prostate can be positive for both P504S (AMACR) and PAS, as well as diastase resistant, thus necessitating caution in interpretation because of its similarity to cancer?

  1. Mucinous metaplasia
  2. Paneth cell-like metaplasia
  3. Squamous metaplasia
  4. Urothelial metaplasia
Board review style answer #1
B. Paneth cell-like metaplasia. Paneth cell-like metaplasia is positive for P504S, similar to cancer. Answer A is incorrect because although mucinous metaplasia is PAS positive and diastase resistant, it is not positive for P504S (AMACR). Answer C is incorrect because squamous metaplasia is negative for both of these markers. Answer D is incorrect because urothelial metaplasia is also negative for these markers.

Comment Here

Reference: Nonneoplastic metaplasia
Board review style question #2

The type of benign prostatic metaplasia shown in the image above is uniquely associated with which condition in the prostate?

  1. Acute inflammation
  2. Granulomatous inflammation
  3. Ischemia or infarction
  4. Radiation therapy
Board review style answer #2
C. Ischemia or infarction. The figure shows squamous metaplasia, which is the only metaplasia associated with ischemia or infarct. Answer A is incorrect because inflammation can be associated with Paneth cell-like metaplasia as well as with squamous metaplasia. Answer B is incorrect because granulomatous inflammation has been associated with Paneth cell-like metaplasia. Answer D is incorrect because radiotherapy can be associated with mucinous, Paneth cell-like or squamous metaplasias. Meanwhile, urothelial metaplasia has no specific associations and is very common.  

Comment Here

Reference: Nonneoplastic metaplasia
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