Prostate

Author: Mikael Häggström ^{[note 1]}

For fragments obtained from transurethral resection of the prostate (TURP):^[1]

• Weigh and measure tissue aggregate in 3 dimensions.
• If weight is less than or equal to 12 gm: Submit entirely in biopsy bags (usually approximately 12 cassettes).
• If weight is more than 12 gm: Submit 12 grams in biopsy bags, and 1 additional cassette per each additional 5 grams.

• For orientation, apply ink or make a cut to one half of the specimen, and possibly a different one to the other side.^[2]

The transverse slices may be cut into quadrants if exceeding laboratory capacity.

  See also: General notes on gross processing

• Prostate adenocarcinoma, including cases of high PSA

• Before microscopy, look at each microscopy slide by eye, to plan the microscopy screening so as to not miss peripheral fragments.
• Screen at low power, and switch to high power when encountering glandular structures that can not otherwise be cleared. Look in particular for those surrounding nerves.
• At least if no cancer is seen, also look for inflammation.^{[notes 1]}

Relatively common and highly specific findings of prostatic adenocarcinoma

^[3]

• 
  Multiple nucleoli (Pictured in an acinar adenocarcinoma, the most common subdiagnosis of prostate adenocarcinoma)
• 
  Eccentric nucleoli^[3] (pictured example has double and eccentric nucleoli).

Specific but relatively rare signs of adenocarcinoma

^{[notes 2]}

• 
  Perineural invasion.^[3] It should be circumferential (as pictured) to count.^[4]

On biopsies, look in particular near the tips for perineural invasion, as it is most likely seen by the capsule. Glands adjacent to and indenting nerves is not sufficient as a diagnostic criterion by itself. Glands partially surrounding a nerve is an indication of carcinoma.^[4]

• Collagenous micronodules for acinar adenocarcinoma^[3]
• Angiolymphatic invasion^[3]
• Extraprostatic extension,^[3] which in biopsies can be diagnosed when tumor cells are located in fatty tissue.

Less specific findings

• 
  Mitoses: also seen in for example high-grade prostatic intraepithelial neoplasia (HGPIN) and prostate inflammation.^[3] Picture shows adenocarcinoma with two mitoses in reactive epithelium.
• 
  Intraluminal blue mucin^[3] (pictured in acinar adenocarcinoma)
• 
  Intraluminal atypical eosinophilic secretions.^[3]
• 
  Intraluminal crystalloids.^[5]
• 
  Uneven distribution and infiltrative pattern of glands
• 
  Glomerulations, for acinar adenocarcinoma, consisting of epithelial proliferations into one or more gland lumina, typically a cribriform tuft with a single attachment to the gland wall.^[4]

• Prominent nucleoli^[3]
• Nuclear enlargement

In case of only less specific findings, consider a Prostatic intraepithelial neoplasia (PIN) or an atypical small acinar proliferation (ASAP).

A PIN is where acini are architecturally benign, but individual cells display atypia. In high-grade PIN (HGPIN), the changes are similar to those of prostate cancer, whereas in low-grade (LGPIN) the changes are milder. Most pathologists do not report the presence of LGPIN.^[7]

An ASAP is a lesion that is probably carcinoma but either lacks definitive diagnostic features, or is too small to be certain (see image below).^[8] It should not be used for benign lesions that are just unusual looking.^[8] In uncertain cases, a diagnosis of adenocarcinoma can be excluded by immunohistochemical detection of basal cells (or confirmed by absence thereof),^[3] such as using the PIN-4 cocktail of stains (which consists of P504S, p63 and high-molecular-weight keratins (HMWK) such as CK5 and CK14).

• 
  Small acinar cell proliferation, with acinar cells with large nuclei, prominent nucleoli (arrows marking two of them) and no certain basal cell lining.
• 
  PIN-4 staining of benign prostate gland and adenocarcinoma

Picture above compares a PIN-4 immunohistochemistry of benign gland (left) and adenocarcinoma (right) using PIN-4. The adenocarcinoma lacks the basal epithelial cells (stained dark brown by p63 and HMWK). Also, in PIN-4 stained samples, adenocarcinoma cells generally display red cytoplasms (stained by AMACR, also known as P504S), while benign glands do not.

• 
  Atrophy is a differential diagnosis to prostate cancer. This example shows gradually increasing simple atrophy from left to right, H&E stain. Crowding and angulation may mimic that of adenocarcinoma, but there is nuclear basophilia rather than atypia, and occasional basal cells can still be seen.
• 
  Also, seminal vesicle glands may mimic prostatic adenocarcinoma by crowded glands with enlarged hyperchromatic and irregular nuclei, but will have inconspicuous nucleoli and coarse refractile golden brown lipofuscin granules.^[9]

• Infoldings in prostate glands.
• Rectum tissue, by transrectal approach such as biopsies.

Example in a normal biopsy:

See Prostate adenocarcinoma article for related reporting.

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