Prostate adenocarcinoma: Difference between revisions

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File:Micrograph of prostate adenocarcinoma with a glomeruloid gland.jpg|Glomerulation.
File:Micrograph of prostate adenocarcinoma with a glomeruloid gland.jpg|Glomerulation.
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*Perineural invasion.<ref name="CruzSantana2016"/> It should be circumferential to count.<ref name=Stanford>{{cite web|url=http://surgpathcriteria.stanford.edu/prostate/adenocarcinoma/|title=Prostatic Adenocarcinoma|website=Stanford Medical School|author=Robert V Rouse MD}} Last update 2/2/16</ref><ref group="notes>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. (Stanford)</ref>
*'''Perineural''' invasion.<ref name="CruzSantana2016"/> It should be circumferential to count.<ref name=Stanford>{{cite web|url=http://surgpathcriteria.stanford.edu/prostate/adenocarcinoma/|title=Prostatic Adenocarcinoma|website=Stanford Medical School|author=Robert V Rouse MD}} Last update 2/2/16</ref><ref group="notes>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. (Stanford)</ref>
*Angiolymphatic invasion<ref name="CruzSantana2016"/>
*'''Angiolymphatic''' invasion<ref name="CruzSantana2016"/>
*Extraprostatic extension <ref name="CruzSantana2016"/>
*'''Extraprostatic''' extension,<ref name="CruzSantana2016"/> which in biopsies can be diagnoses when tumor cells are located in fatty tissue.
;Relatively common and highly specific:<ref name="CruzSantana2016"/>
;Relatively common and highly specific:<ref name="CruzSantana2016"/>
<gallery mode=packed heights=180>
<gallery mode=packed heights=180>

Revision as of 13:59, 14 September 2020

Authors: Mikael Häggström; Authors of integrated Creative Commons article[1] [note 1]

Gross processing

As prostatectomy or biopsy.

Microscopic evaluation

Screening method

  • 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]

Characteristics of adenocarcinoma

Relatively common and highly specific findings of prostatic adenocarcinoma
[1]
Specific but relatively rare signs of adenocarcinoma
[notes 2]

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.[2]

  • Collagenous micronodules for acinar adenocarcinoma[1]
  • Angiolymphatic invasion[1]
  • Extraprostatic extension,[1] which in biopsies can be diagnosed when tumor cells are located in fatty tissue.
Less specific findings
  • Prominent nucleoli[1]
  • Nuclear enlargement

Precancerous lesions

File:Histopathology of high-grade prostatic intraepithelial neoplasia (HGPIN), annotated.jpg
High-grade prostatic intraepithelial neoplasia (HGPIN) with typical features, H&E stain.[4]

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.[5]

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).[6] It should not be used for benign lesions that are just unusual looking.[6] In uncertain cases, a diagnosis of adenocarcinoma can be excluded by immunohistochemical detection of basal cells (or confirmed by absence thereof),[1] 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).

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.

Characteristics

Specific but relatively rare signs of adenocarcinoma
[notes 3]
  • Collagenous micronodules for acinar adenocarcinoma (the most common subdiagnosis)[1]
  • Glomerulations, for acinar adenocarcinoma,[1] consisting of epithelial proliferations into one or more gland lumina, typically a cribriform tuft with a single attachment to the gland wall.[8]
  • Perineural invasion.[1] It should be circumferential to count.[8][notes 4]
  • Angiolymphatic invasion[1]
  • Extraprostatic extension,[1] which in biopsies can be diagnoses when tumor cells are located in fatty tissue.
Relatively common and highly specific
[1]
Less specific findings
  • Prominent nucleoli[1]
  • Nuclear enlargement

In uncertain cases, a diagnosis of malignancy can be discarded by immunohistochemical detection of basal cells,[1] using the PIN-4 cocktail of stains.[notes 5]

Subdiagnoses

File:Prostate cancer types.png
Pie chart of subdiagnoses.[notes 6]

The histopathologic subdiagnosis of prostate cancer has implications for the possibility and methodology of any subsequent Gleason scoring.[9] The most common histopathological subdiagnosis of prostate cancer is acinar adenocarcinoma, constituting 93% of prostate cancers.[10] The most common form of acinar adenocarcinoma, in turn, is "adenocarcinoma, not otherwise specified", also termed conventional, or usual acinar.[11]

Subdiagnosis Relative incidence Image Microscopic characteristics Immunohistochemistry Gleason scoring
Core
biopsy		 Radical prostatectomy
Acinar adenocarcinoma
- 93%[10]		 Adenocarcinoma
(not otherwise specified/
conventional/
usual acinar)[11] 		77%[notes 7] 54%[notes 7] File:Micrograph of prostate cancer with Gleason score 8 (4+4) with glomeruloid glands.jpg
  • Collagenous micronodules[1]
  • Glomerulations[1]
  • May be mixed with other subdiagnoses.
 Tumorous glands:
  • 34βE12- and p63-[10] (+ in adjacent benign glands)[10]
  • Alpha-methylacyl-CoA racemase (AMACR) + (- in adjacent benign glands)[10]
  • PSA+ (>10 ng/ml) in 60% of cases[10]
 As usual
Foamy gland carcinoma 17%[12][notes 6] 13–23%[12][notes 6]
  • Abundant foamy cytoplasm[9]
  • Nuclei may be small and pyknotic - benign-looking[9]
  • Infiltrative pattern
  • Foamy cells:
  • PSA+ and CD68− [9]
  • AMACR+ in 68% of cases[9]
 Based on architecture, discounting foamy cytoplasms[9]
Atrophic carcinoma 2%[12][notes 8] 16%[12][notes 8]
  • Glands lined by cells with scant cytoplasm, resembling atrophy[9]
  • Infiltrative growth[9]
  • Usually admixed with non-atrophic components[9]
 Tumorous glands:
  • 34βE12- and p63- [9]
  • AMACR+ in 70% of cases[9]
 As usual[9]
Pseudohyperplastic carcinoma 2%[12] 11%[12]
  • Large-sized or dilated glands[9]
  • Branching and papillary infolding[9]
  • Tall columnar cells[9]
  • Abundant pale to slight granular luminal cytoplasm[9]
  • Nuclei towards basement membrane[9]
 Tumorous glands:
  • 34βE12- and p63- [9]
  • AMACR+ in 70–83% of cases[9]
 3+3=6[9]
Microcystic carcinoma 11%[12]
  • Cystic dilatation and rounded expansion of malignant glands[13]
  • Lined by flat cells[13]
  • Intraluminal crystalloids, and wispy blue intraluminal mucin[13]
 On (usually) adjacent acinar adeocarcinoma[13]
PIN-like 1.3%[14]
  • Glands lined by ≥2 layers of malignant cells[9]
  • May resemble flat or tufted high-grade PIN, but lacks basal cells[9]
 Tumorous glands:
  • 34βE12- and p63- [9]
 Not recommended[9]
Non acinar
(or mixed acinar/
non-acinar)
adenocarcinoma		 Ductal adenocarcinoma 3% to 12.7%[15][notes 6] File:Micrograph of typical ductal adenocarcinoma of the prostate.jpg
  • Large glands and papillary formations, lined by tall columnar cells, often pseudostratified[9]
  • Papillary, cribriform, individual glands, or solid variants[9]
  • Cytoplasm usually amphophilic[9]
  • Nuclei are large and hyperchromatic, with prominent nucleoli[16]
  • AMACR+ in 77% of cases[9]
  • Usually negative for basal cells stains[9]
Intraductal adenocarcinoma 2.8%[17] File:Micrograph of intraductal carcinoma of the prostate with an infiltrative growth pattern.jpg
H&E and CK5/6
  • Carcinoma cells spanning entire lumen of ducts and acini[18]
  • At least focal preservation of the basal cell layer[18]
Urothelial carcinoma 0.7 to 2.8%[19] File:Urothelial carcinoma in the prostatic urethra, low mag.jpg
  • Umbrella cells are usually present in low-grade tumors[20]
  • Frequently branching fibrovascular cores[20]
  • Frequently fusing of papillae[20]
 Not recommended[9]
Small-cell carcinoma 0.3–2%[21][22][notes 6] File:Micrograph of small-cell carcinoma of the prostate.jpg
  • Small blue cells with scant cytoplasm[9]
  • High nucleus/cytoplasm ratio[9]
  • "salt and pepper" chromatin[9]
  • Nuclear molding[9]
  • Necrosis of single cells, or geographic[9]
  • Smearing artifacts[9]

Half of cases have usual acinar components[9]

Mucinous adenocarcinoma 0.2%[19] File:Micrograph of mucinous adenocarcinoma of the prostate with Gleason score 7 (3 + 4) with individual well-formed glands and minor component of cribriform glands floating in extracellular mucin.jpg
  • ≥25% of tumor shows extracellular mucin[9]
  • Intraluminal mucinous material does not qualify[9]
  • No extraprostatic origin found[9]
 Tumorous glands:
  • 34βE12- and p63-[9]
  • PSA+ and CK8/18+[9]
 4+4=8 for irregular cribriform glands floating in mucin.[9]
Signet-ring adenocarcinoma 0.02%[23] File:Micrograph of signet-ring adenocarcinoma of the prostate.jpg
  • ≥25% of tumor shows signet-ring cells (widely infiltrative cells with optically clear vacuoles displacing the nuclei)[9]
 Tumorous glands: Not recommended[9]
Basal-cell carcinoma 0.01%[24] Basaloid tumor:
  • Scant cytoplasm[9]
  • High nucleus/cytoplasm ratio[9]
  • Irregular or angulated nuclei[9]
  • Euchromatic[9]
  • May have nuclear and cytoplasmic micro-vacuolation[9]
  • Infiltration of adjacent parenchyma[9]

BCC-pattern:

  • Variably sized solid nests, cords, or trabeculae[9]
  • Peripheral palisading[9]
  • p63+ [9]
  • HMCK(34βE12)+[9]
  • Typically CK20−/CK7+, but CK7− in pure solid basal cell nests[9]
  • Bcl-2+, strongly and diffusely[9]
  • Ki-67 nuclear staining in >20%[9]
 Not recommended.[9]

Gleason scoring

File:Gleasonscore.jpg

Rate the dominant, or most common cell morphology (scored 1—5), in addition to the non-dominant cell pattern with the highest grade (scored 1—5).

Staging

Depending on sample type:

  • Multiple biopsy specimens: Adenocarcinoma presence in how many of the biopsies
  • Prostatectomy: Stage by TNM:

From the AJCC 7th edition[25] and International Union Against Cancer (UICC) 7th edition.[26]

Evaluation of the (primary) tumor ('T')
  • TX: cannot evaluate the primary tumor
  • T0: no evidence of tumor
  • T1: tumor present, but not detectable clinically or with imaging
    • T1a: tumor was incidentally found in 5% or less of prostate tissue resected (for other reasons)
    • T1b: tumor was incidentally found in greater than 5% of prostate tissue resected
    • T1c: tumor was found in a needle biopsy performed due to an elevated serum PSA
  • T2: the tumor can be felt (palpated) on examination, but has not spread outside the prostate
    • T2a: the tumor is in half or less than half of one of the prostate gland's two lobes
    • T2b: the tumor is in more than half of one lobe, but not both
    • T2c: the tumor is in both lobes but within the prostatic capsule
  • T3: the tumor has spread through the prostatic capsule (if it is only part-way through, it is still T2)
    • T3a: the tumor has spread through the capsule on one or both sides
    • T3b: the tumor has invaded one or both seminal vesicles
  • T4: the tumor has invaded other nearby structures
Evaluation of the regional lymph nodes ('N')
  • NX: cannot evaluate the regional lymph nodes
  • N0: there has been no spread to the regional lymph nodes
  • N1: there has been spread to the regional lymph nodes
Evaluation of distant metastasis ('M')
  • MX: cannot evaluate distant metastasis
  • M0: there is no distant metastasis
  • M1: there is distant metastasis
    • M1a: the cancer has spread to lymph nodes beyond the regional ones
    • M1b: the cancer has spread to bone
    • M1c: the cancer has spread to other sites (regardless of bone involvement)
Further information: Evaluation

Report

  • Diagnosis
  • Gleason score
  • Extent
  • Prostatectomy: Stage.
  • Prostate biopsies: Number of biopsies where tumor is found.
  • Any perineural or angiolymphatic invasion.

  See also: General notes on reporting


Notes

  1. ↑ Inflammation can explain for example a high PSA value in the absence of adenocarcinoma, so its reporting is usually only needed in such cases.
  2. ↑ "Rare" here refers to prevalence at least in core biopsies.(Cruz 2016)
  3. ↑ "Rare" here refers to prevalence at least in core biopsies.(Cruz 2016)
  4. ↑ 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. (Stanford)
  5. ↑ PIN-4 consists of p504s, CK5, CK14 and p63.
  6. ↑ 6.0 6.1 6.2 6.3 6.4 At least where noted, the numbers include cases where the pattern is found admixed with usual acinar adenocarcinoma.
  7. ↑ 7.0 7.1 Numbers for usual acinar adenocarcinoma do not include mixed patterns with other subdiagnoses.
  8. ↑ 8.0 8.1 Number refers to sporadic atrophic pattern adenocarcinoma.
  1. ↑ For a full list of contributors, see article history. Creators of images are attributed at the image description pages, seen by clicking on the images. See Patholines:Authorship for details.

Main page

References

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 1.15 1.16 1.17 1.18 1.19 1.20 1.21 1.22 1.23 1.24 1.25 Initially largely copied from: Cruz, Andrea O.; Santana, Amanda L. S.; Santos, Andréia C.; Athanazio, Daniel A. (2016). "Frequency of the morphological criteria of prostate adenocarcinoma in 387 consecutive prostate needle biopsies: emphasis on the location and number of nucleoli ". Jornal Brasileiro de Patologia e Medicina Laboratorial. doi:10.5935/1676-2444.20160018. ISSN 1676-2444.  Cite error: Invalid <ref> tag; name "CruzSantana2016" defined multiple times with different content
  2. ↑ 2.0 2.1 2.2 Robert V Rouse MD. Prostatic Adenocarcinoma. Stanford Medical School. Last update 2/2/16
  3. ↑ Svatek, R S; Karam, J A; Rogers, T E; Shulman, M J; Margulis, V; Benaim, E A (2007). "Intraluminal crystalloids are highly associated with prostatic adenocarcinoma on concurrent biopsy specimens ". Prostate Cancer and Prostatic Diseases 10 (3): 279–282. doi:10.1038/sj.pcan.4500954. ISSN 1365-7852. 
  4. ↑ Image by Mikael Häggström, MD. Reference for features:
    - Margaret Sanders, M.B.B.Ch., Murali Varma, M.B.B.S.. High grade prostatic intraepithelial neoplasia (HGPIN). Pathology Outlines. Last author update: 23 February 2021
  5. ↑ Stanley A Brosman, MD. Precancerous Lesions of the Prostate. Medscape. Updated: Feb 26, 2020
  6. ↑ 6.0 6.1 . Prostatic Adenocarcinoma - Atypical Small Acinar Proliferation (ASAP). Stanford Medical School. Retrieved on 2020-09-14.
  7. ↑ Image by Mikael Häggström, MD. Reference for findings: Faryal Shoaib, M.D., Chinedum Okafor, M.D., Y. Albert Yeh, M.D., Ph.D.. Anatomy & histology-seminal vesicles / ejaculatory duct. Pathology Outlines. Last staff update: 20 November 2023
  8. ↑ 8.0 8.1 Robert V Rouse MD. Prostatic Adenocarcinoma. Stanford Medical School. Last update 2/2/16
  9. ↑ 9.00 9.01 9.02 9.03 9.04 9.05 9.06 9.07 9.08 9.09 9.10 9.11 9.12 9.13 9.14 9.15 9.16 9.17 9.18 9.19 9.20 9.21 9.22 9.23 9.24 9.25 9.26 9.27 9.28 9.29 9.30 9.31 9.32 9.33 9.34 9.35 9.36 9.37 9.38 9.39 9.40 9.41 9.42 9.43 9.44 9.45 9.46 9.47 9.48 9.49 9.50 9.51 9.52 9.53 9.54 9.55 9.56 9.57 9.58 9.59 9.60 "The pathology of unusual subtypes of prostate cancer ". Chin. J. Cancer Res. 28 (1): 130–43. February 2016. doi:10.3978/j.issn.1000-9604.2016.01.06. PMID 27041935. 
  10. ↑ 10.0 10.1 10.2 10.3 10.4 10.5 Baig, Faraz A.; Hamid, Amna; Mirza, Talat; Syed, Serajuddaula (2015). "Ductal and Acinar Adenocarcinoma of Prostate: Morphological and Immunohistochemical Characterization ". Oman Medical Journal 30 (3): 162–166. doi:10.5001/omj.2015.36. ISSN 1999768X. 
  11. ↑ 11.0 11.1 . Prostatic Adenocarcinoma. Stanford University School of Medicine. Retrieved on 2019-10-30.
  12. ↑ 12.0 12.1 12.2 12.3 12.4 12.5 12.6 Humphrey, Peter A (2018). "Variants of acinar adenocarcinoma of the prostate mimicking benign conditions ". Modern Pathology 31 (S1): 64–70. doi:10.1038/modpathol.2017.137. ISSN 0893-3952. 
  13. ↑ 13.0 13.1 13.2 13.3 13.4 13.5 Yaskiv, Oksana; Cao, Dengfeng; Humphrey, Peter A. (2010). "Microcystic Adenocarcinoma of the Prostate: A Variant of Pseudohyperplastic and Atrophic Patterns ". The American Journal of Surgical Pathology 34 (4): 556–561. doi:10.1097/PAS.0b013e3181d2a549. ISSN 0147-5185. 
  14. ↑ Zhou, Ming (2018). "High-grade prostatic intraepithelial neoplasia, PIN-like carcinoma, ductal carcinoma, and intraductal carcinoma of the prostate ". Modern Pathology 31 (S1): 71–79. doi:10.1038/modpathol.2017.138. ISSN 0893-3952. 
  15. ↑ "The update of prostatic ductal adenocarcinoma ". Chin. J. Cancer Res. 28 (1): 50–7. February 2016. doi:10.3978/j.issn.1000-9604.2016.02.02. PMID 27041926. 
  16. ↑ Robert V Rouse (2012-01-06). Prostatic Ductal Adenocarcinoma. Stanford University School of Medicine.
  17. ↑ 17.0 17.1 17.2 17.3 Magers, Martin; Kunju, Lakshmi Priya; Wu, Angela (2015). "Intraductal Carcinoma of the Prostate: Morphologic Features, Differential Diagnoses, Significance, and Reporting Practices ". Archives of Pathology & Laboratory Medicine 139 (10): 1234–1241. doi:10.5858/arpa.2015-0206-RA. ISSN 0003-9985. 
  18. ↑ 18.0 18.1 Roberts, Jordan A.; Zhou, Ming; Park, Yong Wok; Ro, Jae Y. (2013). "Intraductal Carcinoma of Prostate: A Comprehensive and Concise Review ". Korean Journal of Pathology 47 (4): 307. doi:10.4132/KoreanJPathol.2013.47.4.307. ISSN 1738-1843. 
  19. ↑ 19.0 19.1 Grignon, David J (2004). "Unusual subtypes of prostate cancer ". Modern Pathology 17 (3): 316–327. doi:10.1038/modpathol.3800052. ISSN 0893-3952. 
  20. ↑ 20.0 20.1 20.2 Robert V Rouse. Papillary Urothelial (Transitional Cell) Carcinoma. Stanford University School of Medicine. Original posting/updates: 10/20/12, 12/29/12
  21. ↑ 0.3%-1%: Page 77 in:Beltran, Antonio (2017). Pathology of the prostate : an algorithmic approach . Cambridge, United Kingdom New York, NY: Cambridge University Press. ISBN 978-1-108-18565-3. OCLC 1011514854. 
  22. ↑ 0.5-2%: Kumar, Kishore; Ahmed, Rafeeq; Chukwunonso, Chime; Tariq, Hassan; Niazi, Masooma; Makker, Jasbir; Ihimoyan, Ariyo (2018). "Poorly Differentiated Small-Cell-Type Neuroendocrine Carcinoma of the Prostate: A Case Report and Literature Review ". Case Reports in Oncology 11 (3): 676–681. doi:10.1159/000493255. ISSN 1662-6575. 
  23. ↑ Wang, Jue; Wang, Fen Wei; Hemstreet, George P. (2011). "Younger Age Is an Independent Predictor for Poor Survival in Patients with Signet Ring Prostate Carcinoma ". Prostate Cancer 2011: 1–8. doi:10.1155/2011/216169. ISSN 2090-3111. 
  24. ↑ Ninomiya, Sahoko; Kawahara, Takashi; Iwashita, Hiromichi; Iwamoto, Genta; Takamoto, Daiji; Mochizuki, Taku; Kuroda, Shinnosuke; Takeshima, Teppei; et al. (2018). "Prostate Basal Cell Carcinoma: A Case Report ". Case Reports in Oncology 11 (1): 138–142. doi:10.1159/000487389. ISSN 1662-6575. 
  25. ↑ American Joint Committee on Cancer. Edge, Stephen B, ed. (2010). AJCC cancer staging manual. (7th ed.). New York: Springer. p. 457–468. ISBN 9780387884400. 
  26. ↑ . TNM | UICC (in en). Union for International Cancer Control. Retrieved on 11 November 2017.

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