A histopathologic diagnosis of prostate cancer is the discernment of whether there is a cancer in the prostate, as well as specifying any subdiagnosis of prostate cancer if possible. The histopathologic subdiagnosis of prostate cancer has implications for the possibility and methodology of any subsequent Gleason scoring. The most common histopathological subdiagnosis of prostate cancer is acinar adenocarcinoma, constituting 93% of prostate cancers. The most common form of acinar adenocarcinoma, in turn, is "adenocarcinoma, not otherwise specified", also termed conventional, or usual acinar adenocarcinoma.
Sampling
The main sources of tissue sampling are prostatectomy and prostate biopsy.
Subdiagnoses - overview
Subdiagnosis Relative incidence Image Microscopic characteristics Immunohistochemistry Gleason scoring Corebiopsy Radical prostatectomy Acinar adenocarcinoma- 93% Adenocarcinoma (not otherwise specified/conventional/usual acinar) 77%Numbers for usual acinar adenocarcinoma do not include mixed patterns with other types. 54% Collagenous micronodules Glomerulations Further information in section below May be mixed with other subdiagnoses. Tumorous glands: 34βE12- and p63- (+ in adjacent benign glands) AMACR+ (- in adjacent benign glands) PSA+ (>10 ng/ml) in 60% of cases As usual Foamy gland carcinoma 17% 13–23% Abundant foamy cytoplasm Nuclei may be small and pyknotic - benign-looking Infiltrative pattern Foamy cells: PSA+ and CD68− AMACR+ in 68% of cases Based on architecture, discounting foamy cytoplasms Atrophic carcinoma 2%Number refers to sporadic atrophic pattern adenocarcinoma. 16% Glands lined by cells with scant cytoplasm, resembling atrophy Infiltrative growth Usually admixed with non-atrophic components Tumorous glands: 34βE12- and p63- AMACR+ in 70% of cases As usual Pseudohyperplastic carcinoma 2% 11% Large-sized or dilated glands Branching and papillary infolding Tall columnar cells Abundant pale to slight granular luminal cytoplasm Nuclei towards basement membrane Tumorous glands: 34βE12- and p63- AMACR+ in 70–83% of cases 3+3=6 Microcystic carcinoma 11% Cystic dilatation and rounded expansion of malignant glands Lined by flat cells Intraluminal crystalloids, and wispy blue intraluminal mucin 34βE12- and p63- AMACR+ On (usually) adjacent acinar adeocarcinoma PIN-like 1.3% Glands lined by ≥2 layers of malignant cells May resemble flat or tufted high-grade PIN, but lacks basal cells Tumorous glands: 34βE12- and p63- Not recommended Non acinar(or mixed acinar/non-acinar) adenocarcinoma Ductal adenocarcinoma 3% to 12.7% Large glands and papillary formations, lined by tall columnar cells, often pseudostratified Papillary, cribriform, individual glands, or solid variants Cytoplasm usually amphophilic Nuclei are large and hyperchromatic, with prominent nucleoli AMACR+ in 77% of cases Usually negative for basal cells stains Intraductal adenocarcinoma 2.8% H&E and CK5/6 Carcinoma cells spanning entire lumen of ducts and acini At least focal preservation of the basal cell layer PSA+ AMACR+ Basal cell markers+ Urothelial carcinoma 0.7 to 2.8% Umbrella cells are usually present in low-grade tumors Original posting/updates: 10/20/12, 12/29/12 Frequently branching fibrovascular cores Frequently fusing of papillae Not recommended Small-cell carcinoma 0.3–2%0.3–1%: Page 77 in:0.5-2%: Small blue cells with scant cytoplasm High nucleus/cytoplasm ratio "salt and pepper" chromatin Nuclear molding Necrosis of single cells, or geographic Smearing artifacts Half of cases have usual acinar components Mucinous adenocarcinoma 0.2% ≥25% of tumor shows extracellular mucin Intraluminal mucinous material does not qualify No extraprostatic origin found Tumorous glands: 34βE12- and p63- PSA+ and CK8/18+ 4+4=8 for irregular cribriform glands floating in mucin. Signet-ring adenocarcinoma 0.02% ≥25% of tumor shows signet-ring cells (widely infiltrative cells with optically clear vacuoles displacing the nuclei) Tumorous glands: 34βE12- and p63- PSA+ Not recommended Basal-cell carcinoma 0.01% Basaloid tumor: Scant cytoplasm High nucleus/cytoplasm ratio Irregular or angulated nuclei Euchromatic May have nuclear and cytoplasmic micro-vacuolation Infiltration of adjacent parenchyma BCC-pattern: Variably sized solid nests, cords, or trabeculae Peripheral palisadingp63+ HMCK(34βE12)+ Typically CK20−/CK7+, but CK7− in pure solid basal cell nests Bcl-2+, strongly and diffusely Ki-67 nuclear staining in >20% Not recommended.
In uncertain cases, a diagnosis of malignancy can be excluded by immunohistochemical detection of basal cells (or confirmed by absence thereof), such as using the PIN-4 cocktail of stains, which targets p63, CK-5, CK-14 and AMACR (latter also known as P504S).
Other prostate cancer tumor markers may be necessary in cases that remain uncertain after microscopy.
Acinar adenocarcinoma These constitute 93% of prostate cancers.
Microscopic characteristics Specific but relatively rare"Rare" here refers to prevalence at least in core biopsies.- Collagenous micronodules Glomerulations, epithelial proliferations into one or more gland lumina, typically a cribriform tuft with a single attachment to the gland wall. Perineural invasion. It should be circumferential Last update 2/2/16Glands adjacent to and indenting nerves is not sufficient as a diagnostic criterion by itself. Glands partially surrounding a nerve is an indication of carcinoma.- Last update 2/2/16 Angiolymphatic invasion Extraprostatic extension
Relatively common and highly specific Multiple nucleoli Eccentric nucleoli
Less specific findings. Mitoses (also seen in for example high-grade prostatic intraepithelial neoplasia (HGPIN) and prostate inflammation). Prominent nucleoli Intraluminal eosinophilic secretion Intraluminal blue mucin
In uncertain cases, a diagnosis of malignancy can be discarded by immunohistochemical detection of basal cells.
Intraductal carcinoma
Intraductal carcinoma of the prostate gland (IDCP), which is now categorised as a distinct entity by WHO 2016, includes two biologically distinct diseases. IDCP associated with invasive carcinoma (IDCP-inv) generally represents a growth pattern of invasive prostatic adenocarcinoma while the rarely encountered pure IDCP is a precursor of prostate cancer."This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/)," The diagnostic criterion of nuclear size at least 6 times normal is ambiguous as size could refer to either nuclear area or diameter. If area, then this criterion could be re-defined as nuclear diameter at least three times normal as it is difficult to visually compare area of nuclei. It is also unclear whether IDCP could also include tumors with ductal morphology. There is no consensus whether pure IDCP in needle biopsies should be managed with re-biopsy or radical therapy. A pragmatic approach would be to recommend radical therapy only for extensive pure IDCP that is morphologically unequivocal for high-grade prostate cancer. Active surveillance is not appropriate when low-grade invasive cancer is associated with IDCP, as such patients usually have unsampled high-grade prostatic adenocarcinoma. It is generally recommended that IDCP component of IDCP-inv should be included in tumor extent but not grade. However, there are good arguments in favor of grading IDCP associated with invasive cancer. WHO 2016 recommends that IDCP should not be graded, but it is unclear whether this applies to both pure IDCP and IDCP-inv.
Ductal adenocarcinoma may have a prominent cribriforming architecture, with glands appearing relatively round, and may thereby mimic intraductal adenocarcinoma, but can be distinguished by the following features: + Differences between ductal and intraductal adenocarcinoma Feature Ductal adenocarcinoma Intraductal adenocarcinoma True fibrovascular cores in micropapillary architecture Present Usually absent Cribriform lumens Lined by pseudostratified, columnar cells Punched out lumens lined by cuboidal cells Basal cell markers Usually negative Usually positive
Further workup Further workup of a diagnosis of prostate cancer includes mainly: Gleason score Prostate cancer staging
Notes
Reference list
Sources