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Review Article | DOI: https://doi.org/10.31579/2767-7370/087
North Manchester General Hospital, Department of Urology, Delaunays Road, M8 5RB, Manchester, United Kingdom.
*Corresponding Author: Anthony Kodzo-Grey Venyo, North Manchester General Hospital, Department of Urology, Delaunays Road, Manchester, M8 5RB. United Kingdom.
Citation: Anthony Kodzo-Grey Venyo, (2024), Adenosis / Atypical adenomatous hyperplasia of Prostate Gland. Review and Update, J New Medical Innovations and Research, 5(2); DOI:10.31579/2767-7370/087
Copyright: © 2024, Anthony Kodzo-Grey Venyo. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Received: 24 January 2024 | Accepted: 01 February 2024 | Published: 07 February 2024
Keywords: atypical adenomatous hyperplasia of prostate; adenosis of prostate; biopsy of prostate; transition zone of prostate; raised serum prostate specific antigen; ultrasound scan
The diagnosis of carcinoma of prostate gland has tended to be challenging because of the existence of lesions that simulate adenocarcinoma of prostate gland. Such a type of prostate lesion is atypical adenomatous hyperplasia (AAH) or adenosis, which represents a proliferation of crowded, small to medium glands with basal cell layer invariably present, but often it has tended to inconspicuous upon routine histopathology of prostate gland examination staining. The importance of the lesion lies in its potential for being misdiagnosed as low-grade adenocarcinoma (Gleason 1 or 2). Atypical adenomatous hyperplasia (AAH) or adenosis of the prostate gland is terminology that is used for a pseudo-neoplastic lesion which can simulate adenocarcinoma of prostate gland in view of its cytological as well as its architectural features. It had previously been iterated that for many years, atypical epithelial lesions of the prostate gland had been known to occur, but much refining of this knowledge had eventually evolved over the last three and half decades. Previously two lesions, prostatic intraepithelial neoplasia (PIN) and AAH, were regarded to be precursors of adenocarcinoma of prostate gland. Nevertheless, PIN has now remained the only well-proven preneoplastic condition with clinical significance. It had been pointed out that AAH is no longer regarded to be a premalignant lesion but rather a benign small glandular process of the transition zone which does mimic acinar adenocarcinoma. In view of the fact that AAH occurs predominantly within the transition zone of prostate gland, which is only rarely sampled in needle biopsy of prostate gland, it has tended to be uncommon to visualise examples of this lesion in biopsy specimens. Nevertheless, as the sampling of the transition zone of the prostate gland had become more frequently undertaken over the past few decades with ultrasound-guided multiple segmental prostate biopsies, as well as radiology-mage guided- targeted prostate biopsies of suspicious lesion with utilisation of also computed tomography scan / magnetic resonance imaging scan, the practicing surgical pathologists needs to be aware of the histopathology examination features of AAH of the prostate in needle biopsy specimens, in order to avoid misinterpretation of AAH of the prostate, which is a benign lesion, as adenocarcinoma of prostate gland. Furthermore, because some patients manifesting with raised serum prostate specific antigen (PSA) levels and negative peripheral zone biopsy may manifest with transition zone adenocarcinoma of prostate gland, sampling of the transition zone of the prostate by needle biopsy and the identification of AAH are likely to increase. If an atypical adenosis hyperplasia (AAH) or adenosis is misdiagnosed as localised adenocarcinoma of the prostate gland, then the individual found to have AAH could be inadvertently treated as a treatment of curative intent of either radical prostatectomy or radical radiotherapy that would represent unnecessary treatment over-aggressive treatment associated with more significant side effects and complications. Nevertheless, if a correct diagnosis of AAH of the prostate gland is established then the patient would not need any surgical or radiotherapy. A number of cases of AAH of prostate gland also tend to diagnosed specimens of trans-urethral resection of prostate gland specimens and prostatectomy specimens. Diagnosis of AAH of prostate gland tends to be diagnosed based upon the histopathology and immunohistochemistry staining features of specimens of the prostate gland, The pathologist also needs to be aware of which antibody staining agents that need to be used in order to clearly confirm the diagnosis of AAH of prostate gland and this has been detailed out in the ensuing article.
Atypical adenomatous hyperplasia (AAH) or adenosis of the prostate is a pseudo-neoplastic lesion that can mimic prostate adenocarcinoma because of its cytologic and architectural features [1-4]. For many years, atypical epithelial lesions of the prostate have been known to occur, but much refining of this knowledge has evolved over the last two decades. Initially two lesions, prostatic intraepithelial neoplasia, and AAH, were assumed to be precursors of prostatic adenocarcinoma [1-4]. Nevertheless, PIN now remains as the only well-proven preneoplastic condition with clinical significance. AAH is now, no longer regarded a premalignant lesion but instead a benign small glandular process of the transition zone which simulates acinar adenocarcinoma [1-4]. Since AAH occurs predominantly within the transition zone, which is only rarely sampled during the undertaking of needle biopsy of prostate gland, it is uncommon to see examples of this lesion in biopsy specimens. Nevertheless, as the sampling of the transition zone of the prostate has become more frequent recently with ultrasound-guided multiple segmental prostate biopsies [1,5] the practicing surgical pathologists needs to be aware of the histological features of AAH of the prostate in needle biopsy specimens, in order to avoid misinterpretation of AAH of the prostate gland, which is a benign lesion, rather than adenocarcinoma of prostate gland. Furthermore, because some patients who are found to have raised serum prostate specific antigen levels and negative peripheral zone biopsy may manifest with transition zone prostatic adenocarcinoma, sampling of the transition zone of the prostate by needle biopsy and the identification of AAH are likely to increase [1,5]. The ensuing article is divided into two parts (A) which has discussed general overview aspects of Adenosis / atypical adenomatous hyperplasia and (B) Miscellaneous narrations and discussions from some case reports, case series and studies related to Adenosis / atypical adenomatous hyperplasia.
To review and update the literature on Adenosis / atypical adenomatous hyperplasia.
Internet data bases were searched including: Google, Goggle scholar, Yahoo, and PubMed. The search words that were used included: Adenosis / atypical adenomatous hyperplasia.; Adenosis of prostate gland, atypical adenomatous hyperplasia of prostate gland, prostatic adenosis; and prostatic atypical hyperplasia. Thirty-five (35) references were identified which were used to wite the article which has been divided into two parts: (A) which has discussed general overview aspects of Adenosis / atypical adenomatous hyperplasia and (B) Miscellaneous narrations and discussions from some case reports, case series and studies related to Adenosis / atypical adenomatous hyperplasia
[A] OVERVIEW
Definition / general statement [6]
Essential features [6]
Terminology [6]
Epidemiology [6]
Sites [6]
Pathophysiology [6]
Clinical features [6]
Diagnosis [6]
Radiology description [6]
Prognostic factors [6]
Treatment [6]
Microscopic (histologic) description [6]
Positive stains [6]
Negative stains [6]
Molecular / cytogenetics description [6]
Differential diagnosis [6]
Verhoef et al. [7] stated the following:
With regard to the materials and methods as well as the results of their study, Verhoef et al. [7] iterated the following:
Verhoef et al. [7] concluded that various prostate epithelial lesions might simulate malignancy on H&E slides, their three-dimensional architecture is acinar and clearly different from the tubular structure of prostate cancer, with adenosis as an exception.
Netto and Epstein. [8] stated that prostate needle biopsy currently is the gold standard method for the diagnosis, management, and prognosis of prostate cancer as well as that obtaining an accurate diagnosis is crucial for pursuing proper patient management. Netto and Epstein. [8] in their article summated the histology examination mimickers of prostate carcinoma by highlighting microscopic features that are helpful to reach a correct diagnosis and emphasizing potential diagnostic pitfalls. This article would provide additional educational material for readers.
Humphrey [9] stated the following:
Humphrey [9] summarised the results as follows:
De Visschere et al. [15] undertook a study to identify the multiparametric magnetic resonance imaging (mpMRI) characteristics of normal, benign and malignant conditions in the prostate. De Visschere et al. [15] reported the following:
De Visschere et al. [15] summarized the results as follows:
De Visschere et al. [15] made the following conclusions:
Bettendorf et al. [16] stated the following:
Bettendorf et al. [16] undertook a study to analyse AAH, accompanying prostate carcinomas and carcinomas of the transitional zone after microdissection using comparative genomic hybridization (CGH) and multipelx-PCR with 10 microsatellite polymorphic markers. Bettendorf et al. [16] iterated that in every case non-neoplastic prostatic tissue was investigated for the same allelic imbalances. Bettendorf et al. [16] summarised the results as follows:
Bettendorf et al. [16] concluded that their findings had supported the idea that AAH does not seem to be linked closely to PC and should not be considered as an obligate premalignant lesion.
Lotan et al. [17] stated the following:
Lotan et al. [17] studied 60 cases of DAPZ on needle biopsy in their consult practice from 2001 to 2007. Lotan et al. [17] summarised their results as follows:
Lotan et al. [17] concluded that their findings had suggest that DAPZ should be considered a risk factor for prostate cancer and that patients with this finding should be followed closely and re-biopsied.
Enciu et al. [18] stated the following:
Enciu et al. [18] reported the case of a male patient, who had undergone a transurethral prostatic resection surgery. Histopathology examination of the specimen had shown benign prostatic hyperplasia with a focus of crowded glands with a nodular appearance. The presence of basal cell was assessed utilising high molecular-weight cytokeratin (HMWCK), clone 34βE12 and p63 immunostaining, which revealed discontinuous positive immunostaining. In adenocarcinomas, the basal cell layer was absent. Enciu et al. [18] concluded that their case had highlighted the usefulness of 34βE12 antibodies, avoiding a false positive diagnosis of cancer, with negative consequences on the patient's psychological condition and treatment costs. Enciu et al. [18] had recommended the follow-up of the patient.
Hameed et al. [19] stated that the differential diagnoses of prostatic carcinoma and bladder epithelial neoplasms include several histological mimics that should be known to avoid misdiagnosis. Hameed et al. [19] discussed pseudo-neoplastic lesions of the prostate gland and urinary bladder that could potentially be confused with carcinoma of the prostate gland and urinary bladder epithelial neoplasms, respectively, with specific focus on their distinguishing histopathologic features. Hameed et al. [19] utilised relevant literature and author’s experience.
Hameed et al. [19] made the ensuing conclusions:
Beltran et al. [20] stated the following in 2019:
Lopez Beltran et al. [20] stated that diagnostic biopsies in 1080 cases and transurethral resection of prostate specimens in 314 cases from 1394 men with clinically localized prostate cancer diagnosed within the United Kingdom but treated conservatively between 1990 and 2003 were reviewed by a panel of 3 genitourinary pathologists. Lopez Beltran et al. [20 also stated that thirty-five cases were excluded for being potentially incomplete. Out of the remaining 1359, 30 (2.2%) were reassigned to a non-malignant category (26 benign and 4 suspicious for malignancy). IHC had been originally performed on 7 of these. The reasons for the errors were recorded on each case as follows: adenosis (19), partial atrophy (3), prostatic intraepithelial neoplasia (2), seminal vesicle epithelium (1), and hyperplasia (1). Follow-up of these men had revealed only one prostate cancer-related death, possibly due to unsampled tumour. Lopez Beltran et al. [20] made the ensuing conclusions:
Herawi et al. [21] undertook a study to determine the incidence of various benign mimickers of adenocarcinoma of prostate gland most commonly encountered in a busy consultation practice. Herawi et al. [21] reported that all prostate needle biopsies from the consult service of one of the authors were prospectively evaluated over a 7-month period. Only cases with foci where the contributor questioned malignancy and which upon expert review the entire case was determined to be benign were included in the study. Herawi et al. [21] summarised the results as follows:
Herawi et al. [21] stated the following:
Gaudin et al. [22] stated the following:
Gaudin et al. [22] made the following conclusions:
Phillips et al. [23] stated the following:
Gaudin et al. [24] stated that following:
Doll et al. [25] iterated the ensuing:
Doll et al. [25] analysed DNA from 25 micro-dissected AAH lesions for allelic imbalance as compared to matched normal DNA, using one marker each from chromosome arms 1q, 6q, 7q, 10q, 13q, 16q, 17p, 17q, and 18q, and 19 markers from chromosome 8p. Doll et al. [25] observed 12% allelic imbalance, with loss only within chromosome 8p11–12. Doll et al. [25] stated the following:
Cheng et al. [26] stated the following:
Cheng et al. [26] undertook a study, to investigate telomere shortening in AAH (in a total of 93 cases), high-grade prostatic intraepithelial neoplasia (HGPIN) (in 68 cases), and prostatic adenocarcinoma (PCA) (in 70 cases) using quantitative fluorescence in situ hybridization. Cheng et al. [26] summarised their results as follows:
Cheng et al. [26] concluded that their findings had indicated that a subset of AAH lesions have telomere shortening and AMACR expression, suggesting that these foci may be precursors for PCA.
Zhang et al. [27] stated that they had analysed One hundred twenty-one AAH foci from 101 patients who had undergone transurethral prostatic resection or prostatectomy immunohistochemically for AMACR, high molecular weight cytokeratin 34βE12, and p63 expression by a triple antibody (PIN4) cocktail stain. Zhang et al. [27] summarised the results as follows:
Zhang et al. [27] made the following conclusions:
MZ [28] stated the following:
MZ [28] summarised the results as follows:
MZ [28] made the ensuing conclusions:
Armah and Parwani [1] reported a 62-year-old man, who was referred to his urologist for symptoms of urinary tract obstruction and an elevated serum prostate-specific antigen (PSA) level of 3.61 ng/mL. He underwent digital rectal examination and ultrasound scan which demonstrated an ill-defined nodule within his prostate gland that was suggestive of malignancy. A needle biopsy of the prostate lesion was undertaken. The histology section of one needle biopsy was typified at low-power examination by the replacement of normal prostatic tissue by a proliferation of haphazardly arranged glands, which were partially arranged in an ill-defined nodule. The lesions had an infiltrative aspect at their edge, but the glands were noted not to be admixed with normal prostatic acini. At medium power, the proliferating glands were found to be often slit-like, variably sized and shaped, alternating small and rounded acini with elongated and branching ones (see Figures 1A and 1B). Occasional solid nests and cords could be seen. The atypical acini were noted to be lined by epithelial secretory cells with clear eosinophilic cytoplasm (see Figure 1C). The nuclei were noted to be regular, rounded to oval, and slightly larger than those of the adjacent normal prostatic acini. There were inconspicuous nucleoli. There were a few focally prominent basally located cells with dense amphophilic cytoplasm. Eosinophilic crystalloids were present within some acinar lumina (see Figure 1C and 1D).
Figure 1
Figure 1: Histologic (hematoxylin-eosin) findings of atypical adenomatous hyperplasia of the prostate. (A) Crowded haphazardly arranged variably sized glands with infiltrative appearance of glands at the edges. Original magnification × 200. (B) Predominantly small glands lined by epithelial secretory cells with clear eosinophilic cytoplasm and minimal cytological atypia. Original magnification × 400. (C) Predominantly large glands lined by epithelial secretory cells with clear eosinophilic cytoplasm and minimal cytological atypia. Original magnification × 400. (D) Predominantly large glands lined by epithelial secretory cells with clear eosinophilic cytoplasm, minimal cytological atypia with inconspicuous nucleoli, few focally prominent basally located cells with dense amphophilic cytoplasm, and luminal eosinophilic crystalloids. Original magnification × 600. Reproduced from [1] Under the Creative Commons Attribution License.
Immunohistochemistry (IHC) staining studies revealed strong reactivity for alpha-methylacyl-coenzyme A-racemase (AMACR) in both small and large glands (see Figures 2A and 2B), patchy reactivity for p63 (see figure 2C) and patchy reactivity for high-molecular-weight cytokeratin CK903/34βE12 (see figure 2D).
Figure 2: Immunohistochemical findings of atypical adenomatous hyperplasia of the prostate. (A) Strong reactivity for alpha-methylacyl-coenzyme A-racemase in predominantly small glands. Original magnification × 200. (B) Strong reactivity for alpha-methylacyl-coenzyme A-racemase in predominantly large glands. Original magnification × 200. (C) Patchy reactivity for p63 in both small and large glands. Original magnification × 200. (D) Patchy reactivity for high-molecular-weight cytokeratin CK903/34βE12 in both small and large glands. Original magnification × 200.
The final histopathology diagnosis was benign prostatic tissue with a focus of florid AAH. Two subsequent follow-up prostate needle biopsies were undertaken six months and 12 months later both showed benign prostatic tissue with atrophic changes.
Armah and Parwani [1] made the ensuing educative narrative discussions:
While circumstantial evidence exists, there is lack of proof of a relationship between AAH and adenocarcinoma. It has been suggested that AAH is a precursor of some low-grade transition zone carcinomas but the lack of an increased prevalence of AAH in prostate glands with transition zone carcinoma argues against this hypothesis. Clearly, there is less evidence linking AAH to carcinoma than there is for high-grade PIN and cancer. Therefore, the major importance of AAH is its potential for being misdiagnosed as adenocarcinoma. Biochemical and molecular analyses of AAH have generated inconclusive results. There is limited data that AAH has a proliferation rate higher than hyperplasia but lower than adenocarcinoma [2,29,30,34]. By the use of fluorescent in situ hybridization analysis, chromosomal anomalies were seen in only 9% of AAH cases, compared with 55% of prostatic adenocarcinoma cases. [34]. Two independent studies showed that AAH contains genetic alterations commonly found in early prostatic carcinoma, with changes being reported in 47% or 12% of AAH cases, respectively [25,30]. Recent cytogenetic analyses have detected abnormalities of chromosome 8 in a very small proportion (4–7%) of AAH cases [29,30]. The recent finding of molecular alterations in AAH including immunoreactivity for AMACR, a marker linked to prostate adenocarcinoma, suggests that at least a subset of AAH cases might be related to prostate carcinoma of the transition zone [13, 25,34].
The widespread use of PSA screening has led to an increase in prostate needle biopsies and, subsequently, an increase in earlier detection of prostate carcinoma. This trend has also led to an increase in the number of equivocal diagnoses on prostate biopsy specimens. Surgical pathologists must make critical decisions on an increasing number of prostate needle biopsy specimens with only small foci of atypical glands. In this setting, the mimics of prostate cancer must be distinguished from a small focus of adenocarcinoma. The distinction of benign small acinar proliferations (benign mimickers of cancer) from atypical acinar proliferations suspicious for cancer is crucial, since the subsequent clinical approach is different. Biopsies harbouring a small focus of atypical glands frequently represent an under-sampled cancer and a subsequent biopsy will show cancer in up to 50% of cases [35]. In contrast, following a diagnosis of benign mimickers of cancer (such as atrophy or AAH), a re-biopsy is usually not indicated.
Armah and Parwani [1] made the following conclusions:
Acknowledgements to: Diagnostic Pathology, Bio Med Central and The Springer Nature Shared It content-sharing initiative for granting permission for reproduction of figures and contents of their journal article under copyright: This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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Dear Dr. Jessica Magne, Editorial Coordinator 0f Clinical Cardiology and Cardiovascular Interventions, The review process for the article “The Handling of Anti-aggregants and Anticoagulants in the Oncologic Heart Patient Submitted to Surgery” was extremely rigorous and detailed. From the initial submission to the final acceptance, the editorial team at the “Journal of Clinical Cardiology and Cardiovascular Interventions” demonstrated a high level of professionalism and dedication. The reviewers provided constructive and detailed feedback, which was essential for improving the quality of our work. Communication was always clear and efficient, ensuring that all our questions were promptly addressed. The quality of the “Journal of Clinical Cardiology and Cardiovascular Interventions” is undeniable. It is a peer-reviewed, open-access publication dedicated exclusively to disseminating high-quality research in the field of clinical cardiology and cardiovascular interventions. The journal's impact factor is currently under evaluation, and it is indexed in reputable databases, which further reinforces its credibility and relevance in the scientific field. I highly recommend this journal to researchers looking for a reputable platform to publish their studies.
Dear Editorial Coordinator of the Journal of Nutrition and Food Processing! "I would like to thank the Journal of Nutrition and Food Processing for including and publishing my article. The peer review process was very quick, movement and precise. The Editorial Board has done an extremely conscientious job with much help, valuable comments and advices. I find the journal very valuable from a professional point of view, thank you very much for allowing me to be part of it and I would like to participate in the future!”
Dealing with The Journal of Neurology and Neurological Surgery was very smooth and comprehensive. The office staff took time to address my needs and the response from editors and the office was prompt and fair. I certainly hope to publish with this journal again.Their professionalism is apparent and more than satisfactory. Susan Weiner
My Testimonial Covering as fellowing: Lin-Show Chin. The peer reviewers process is quick and effective, the supports from editorial office is excellent, the quality of journal is high. I would like to collabroate with Internatioanl journal of Clinical Case Reports and Reviews.
My experience publishing in Psychology and Mental Health Care was exceptional. The peer review process was rigorous and constructive, with reviewers providing valuable insights that helped enhance the quality of our work. The editorial team was highly supportive and responsive, making the submission process smooth and efficient. The journal's commitment to high standards and academic rigor makes it a respected platform for quality research. I am grateful for the opportunity to publish in such a reputable journal.
My experience publishing in International Journal of Clinical Case Reports and Reviews was exceptional. I Come forth to Provide a Testimonial Covering the Peer Review Process and the editorial office for the Professional and Impartial Evaluation of the Manuscript.
