Prostate adenocarcinoma

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Author: Mikael Häggström [notes 1]

Comprehensiveness

On this resource, the following formatting is used for comprehensiveness:

  • Minimal depth
  • (Moderate depth)
  • ((Comprehensive))

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 2]

Characteristics

Relatively common and highly specific
[1]

  • Multiple nucleoli (Pictured in an acinar adenocarcinoma, the most common subdiagnosis of prostate adenocarcinoma)

  • Eccentric nucleoli[1] (pictured example has double and eccentric nucleoli).

Specific but relatively rare signs of adenocarcinoma
[notes 3]

  • Perineural invasion.[1] It should be circumferential (as pictured) to count.[2][notes 4]

  • Collagenous micronodules for acinar adenocarcinoma[1]
  • Angiolymphatic invasion[1]
  • Extraprostatic extension,[1] which in biopsies can be diagnoses 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.[1] Picture shows adenocarcinoma with two mitoses in reactive epithelium.

  • Intraluminal blue mucin[1] (pictured in acinar adenocarcinoma)

  • Intraluminal atypical eosinophilic secretions.[1]

  • Intraluminal crystalloids.[3]

  • 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.[2]

  • Prominent nucleoli[1]
  • Nuclear enlargement

Precancerous lesions

Histopathology of a small acinar cell proliferation, with acinar cells with large nuclei, prominent nucleoli (arrows marking two of them) and no certain basal cell lining.

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.[4]

An ASAP is a lesion that is probably carcinoma but either lacks definitive diagnostic features, or is too small to be certain.[5] It should not be used for benign lesions that are just unusual looking.[5] 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).

PIN-4 staining of benign prostate gland and adenocarcinoma.jpg

Picture at left 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.

Subdiagnoses

Pie chart of subdiagnoses.[notes 5]

The histopathologic subdiagnosis of prostate cancer has implications for the possibility and methodology of any subsequent Gleason scoring.[6] The most common histopathological subdiagnosis of prostate cancer is acinar adenocarcinoma, constituting 93% of prostate cancers.[7] The most common form of acinar adenocarcinoma, in turn, is "adenocarcinoma, not otherwise specified", also termed conventional, or usual acinar.[8]

Subdiagnosis Relative incidence Image Microscopic characteristics Immunohistochemistry Gleason scoring
Core
biopsy		 Radical prostatectomy
Acinar adenocarcinoma
- 93%[7]		 Adenocarcinoma
(not otherwise specified/
conventional/
usual acinar)[8] 		77%[notes 6] 54%[notes 6] 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-[7] (+ in adjacent benign glands)[7]
  • Alpha-methylacyl-CoA racemase (AMACR) + (- in adjacent benign glands)[7]
  • PSA+ (>10 ng/ml) in 60% of cases[7]
 As usual
Foamy gland carcinoma 17%[9][notes 5] 13–23%[9][notes 5]
  • Abundant foamy cytoplasm[6]
  • Nuclei may be small and pyknotic - benign-looking[6]
  • Infiltrative pattern
  • Foamy cells:
  • PSA+ and CD68− [6]
  • AMACR+ in 68% of cases[6]
 Based on architecture, discounting foamy cytoplasms[6]
Atrophic carcinoma 2%[9][notes 7] 16%[9][notes 7]
  • Glands lined by cells with scant cytoplasm, resembling atrophy[6]
  • Infiltrative growth[6]
  • Usually admixed with non-atrophic components[6]
 Tumorous glands:
  • 34βE12- and p63- [6]
  • AMACR+ in 70% of cases[6]
 As usual[6]
Pseudohyperplastic carcinoma 2%[9] 11%[9]
  • Large-sized or dilated glands[6]
  • Branching and papillary infolding[6]
  • Tall columnar cells[6]
  • Abundant pale to slight granular luminal cytoplasm[6]
  • Nuclei towards basement membrane[6]
 Tumorous glands:
  • 34βE12- and p63- [6]
  • AMACR+ in 70–83% of cases[6]
 3+3=6[6]
Microcystic carcinoma 11%[9]
  • Cystic dilatation and rounded expansion of malignant glands[10]
  • Lined by flat cells[10]
  • Intraluminal crystalloids, and wispy blue intraluminal mucin[10]
 On (usually) adjacent acinar adeocarcinoma[10]
PIN-like 1.3%[11]
  • Glands lined by ≥2 layers of malignant cells[6]
  • May resemble flat or tufted high-grade PIN, but lacks basal cells[6]
 Tumorous glands:
  • 34βE12- and p63- [6]
 Not recommended[6]
Non acinar
(or mixed acinar/
non-acinar)
adenocarcinoma		 Ductal adenocarcinoma 3% to 12.7%[12][notes 5] Micrograph of typical ductal adenocarcinoma of the prostate.jpg
  • Large glands and papillary formations, lined by tall columnar cells, often pseudostratified[6]
  • Papillary, cribriform, individual glands, or solid variants[6]
  • Cytoplasm usually amphophilic[6]
  • Nuclei are large and hyperchromatic, with prominent nucleoli[13]
  • AMACR+ in 77% of cases[6]
  • Usually negative for basal cells stains[6]
Intraductal adenocarcinoma 2.8%[14] 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[15]
  • At least focal preservation of the basal cell layer[15]
Urothelial carcinoma 0.7 to 2.8%[16] Urothelial carcinoma in the prostatic urethra, low mag.jpg
  • Umbrella cells are usually present in low-grade tumors[17]
  • Frequently branching fibrovascular cores[17]
  • Frequently fusing of papillae[17]
 Not recommended[6]
Small-cell carcinoma 0.3–2%[18][19][notes 5] Micrograph of small-cell carcinoma of the prostate.jpg
  • Small blue cells with scant cytoplasm[6]
  • High nucleus/cytoplasm ratio[6]
  • "salt and pepper" chromatin[6]
  • Nuclear molding[6]
  • Necrosis of single cells, or geographic[6]
  • Smearing artifacts[6]

Half of cases have usual acinar components[6]

Mucinous adenocarcinoma 0.2%[16] 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[6]
  • Intraluminal mucinous material does not qualify[6]
  • No extraprostatic origin found[6]
 Tumorous glands:
  • 34βE12- and p63-[6]
  • PSA+ and CK8/18+[6]
 4+4=8 for irregular cribriform glands floating in mucin.[6]
Signet-ring adenocarcinoma 0.02%[20] 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)[6]
 Tumorous glands: Not recommended[6]
Basal-cell carcinoma 0.01%[21] Basaloid tumor:
  • Scant cytoplasm[6]
  • High nucleus/cytoplasm ratio[6]
  • Irregular or angulated nuclei[6]
  • Euchromatic[6]
  • May have nuclear and cytoplasmic micro-vacuolation[6]
  • Infiltration of adjacent parenchyma[6]

BCC-pattern:

  • Variably sized solid nests, cords, or trabeculae[6]
  • Peripheral palisading[6]
  • p63+ [6]
  • HMCK(34βE12)+[6]
  • Typically CK20−/CK7+, but CK7− in pure solid basal cell nests[6]
  • Bcl-2+, strongly and diffusely[6]
  • Ki-67 nuclear staining in >20%[6]
 Not recommended.[6]

Gleason scoring

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).

  • Gleason pattern 6 (3+3).jpg

  • Gleason pattern 7 (3+4).jpg

  • Gleason pattern 8 (4+4).jpg

  • Gleason pattern 9 (4+5).jpg

  • Gleason pattern 10 (5+5).jpg

Gleason score is as follows:[22]

  • Gleason score ≤3: Only individual discrete well-formed glands
  • Gleason score 4: Poorly-formed, fused and/or cribriform glands
  • Gleason score 5: Lacks gland formation, or has necrosis

  • Gleason score 6 (3+3)

  • Cribriform pattern: Gleason grade 4

  • Gleason score 7 (3+4) with minor component of cribriform glands

  • Gleason score 8 (4+4) with glomeruloid glands

  • Gleason score 8 (4+4) with irregular cribriform glands

  • Gleason score 8 (4+4) with fused glands with cytoplasmic vacuoles

  • Gleason score 8 (4+4) with poorly-formed glands

  • Gleason score 9 (4+5) with cribriform glands, some with necrosis

  • Gleason score 10 (5+5) with cords of cells

  • Gleason score 10 (5+5) with individual cells

  • Gleason score 10 (5+5) with solid sheets of cells

Grade group

(In a moderately comprehensive report, also state the overall grade group for the adenocarcinoma:[22]

  • Grade group 1 (Gleason score ≤6) - Only individual discrete well-formed glands
  • Grade group 2 (Gleason score 3+4=7) - Predominantly well-formed glands with a lesser component of poorly-formed, fused and/or cribriform glands
  • Grade group 3 (Gleason score 4+3=7) - Predominantly poorly-formed, fused, and/or cribriform glands with a lesser component of well-formed glands
  • Grade group 4 (Gleason score 8), either of the following
  • Only poorly-formed, fused and/or cribriform glands
  • Predominantly well-formed glands with a lesser component that lacks glands
  • Predominantly lacking glands with a lesser component of well-formed glands
  • Grade group 5 (Gleason scores 9-10): Any area that lacks gland formation, or with necrosis)

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[23] and International Union Against Cancer (UICC) 7th edition.[24]

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, and optionally grade group
  • Extent
  • Prostatectomy: Stage.
  • Prostate biopsies: Number of biopsies where tumor is found, and percentage of involvement in those cases.<ref group=notes>Percentage of involvement can be estimate by first estimated what percentage of the field-of-view diameter the tumorous area occupies, or how many field-of-view diameters it occupies, divided by how many field-of-view diameters the entire biopsy occupies.
  • Any perineural or angiolymphatic invasion.
  • ((Any inflammation.[notes 2]))
(Prostate, left apex, needle biopsy:)
Prostatic adenocarcinoma, Gleason score 3+3 = 6 (grade group 1), involving 30% of out of one core.

If the microscopy and gross description give discordant number of cores, you may use the gross number. For cancers, generally include a synoptic report, such as per College of American Pathologists (CAP) protocols at cap.org/protocols-and-guidelines.

See also: General notes on reporting

Notes

  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.
  2. ↑ 2.0 2.1 Inflammation can explain for example a high PSA value in the absence of adenocarcinoma, so its reporting is usually only needed in such cases.
  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. ↑ 5.0 5.1 5.2 5.3 5.4 At least where noted, the numbers include cases where the pattern is found admixed with usual acinar adenocarcinoma.
  6. ↑ 6.0 6.1 Numbers for usual acinar adenocarcinoma do not include mixed patterns with other subdiagnoses.
  7. ↑ 7.0 7.1 Number refers to sporadic atrophic pattern adenocarcinoma.

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 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. 
    Attribution 4.0 International (CC BY 4.0) license
  2. ↑ 2.0 2.1 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. ↑ Stanley A Brosman, MD. Precancerous Lesions of the Prostate. Medscape. Updated: Feb 26, 2020
  5. ↑ 5.0 5.1 . Prostatic Adenocarcinoma - Atypical Small Acinar Proliferation (ASAP). Stanford Medical School. Retrieved on 2020-09-14.
  6. ↑ 6.00 6.01 6.02 6.03 6.04 6.05 6.06 6.07 6.08 6.09 6.10 6.11 6.12 6.13 6.14 6.15 6.16 6.17 6.18 6.19 6.20 6.21 6.22 6.23 6.24 6.25 6.26 6.27 6.28 6.29 6.30 6.31 6.32 6.33 6.34 6.35 6.36 6.37 6.38 6.39 6.40 6.41 6.42 6.43 6.44 6.45 6.46 6.47 6.48 6.49 6.50 6.51 6.52 6.53 6.54 6.55 6.56 6.57 6.58 6.59 6.60 "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. 
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 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. 
  8. ↑ 8.0 8.1 . Prostatic Adenocarcinoma. Stanford University School of Medicine. Retrieved on 2019-10-30.
  9. ↑ 9.0 9.1 9.2 9.3 9.4 9.5 9.6 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. 
  10. ↑ 10.0 10.1 10.2 10.3 10.4 10.5 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. 
  11. ↑ 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. 
  12. ↑ "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. 
  13. ↑ Robert V Rouse (2012-01-06). Prostatic Ductal Adenocarcinoma. Stanford University School of Medicine.
  14. ↑ 14.0 14.1 14.2 14.3 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. 
  15. ↑ 15.0 15.1 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. 
  16. ↑ 16.0 16.1 Grignon, David J (2004). "Unusual subtypes of prostate cancer ". Modern Pathology 17 (3): 316–327. doi:10.1038/modpathol.3800052. ISSN 0893-3952. 
  17. ↑ 17.0 17.1 17.2 Robert V Rouse. Papillary Urothelial (Transitional Cell) Carcinoma. Stanford University School of Medicine. Original posting/updates: 10/20/12, 12/29/12
  18. ↑ 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. 
  19. ↑ 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. 
  20. ↑ 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. 
  21. ↑ 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. 
  22. ↑ 22.0 22.1 . New Contemporary Prostate Cancer Grading System. Johns Hopkins University, Department of Pathology. Retrieved on 2020-09-21.
  23. ↑ American Joint Committee on Cancer. Edge, Stephen B, ed. (2010). AJCC cancer staging manual. (7th ed.). New York: Springer. p. 457–468. ISBN 9780387884400. 
  24. ↑ . TNM | UICC (in en). Union for International Cancer Control. Retrieved on 11 November 2017.
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