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ORIGINAL ARTICLE  
Year : 2020  |  Volume : 63  |  Issue : 3  |  Page : 423-426
Eosinophilic metaplasia in transurethral resection of the prostate


1 Department of General and Clinical Pathology, Medical University - Plovdiv, Plovdiv, Bulgaria
2 Department of Pathology, Jossigny Hospital, Jossigny, France; Department of General and Clinical Pathology, Medical University - Plovdiv, Plovdiv, Bulgaria
3 Medical Biology, Medical University - Plovdiv; Technological Center for Emergency Medicine, Plovdiv, Bulgaria

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Date of Submission29-Jul-2019
Date of Decision05-Nov-2019
Date of Acceptance19-Nov-2019
Date of Web Publication7-Aug-2020
 

   Abstract 


Background: To investigate prostatic eosinophilic metaplasia (EM) in a large series of cases and their relationship with the basic prostate pathology in TURP-material: benign prostatic hyperplasia (BPH), National Institutes of Health category IV prostatitis (also called histologic prostatitis or HP), and prostatic adenocarcinoma (PCa). Aim: The relation between EM and basic prostate pathology: BPH, PCa, and HP. Materials and Methods: Around 61 consecutive TURP-specimens were reviewed for the presence of EM. The tissue sections were stained routinely with hematoxylin-eosin (HE), hematoxylin-phloxine-saffron (HPS), and periodic acid-Schiff's procedure. Simultaneously BPH, HP, and PCa were evaluated. Results: We found EM in 55.7% of TURP-specimens. EM is located more often in the ductal epithelium (58.8%) and is usually focal (73.5%) and in small groups (88.2%) of secretory luminal cells. They are associated with BPH and with a variable degree of HP in all cases. However, there is no association with PCa. Eosinophilic cytoplasmic granules in EM are better visualized with HPS. Zones induced by tissue electrocoagulation which mimic EM, are seen in the periphery of TURP-fragments. Conclusion: EM in prostate is presented by the presence of eosinophilic cytoplasmic granules in benign secretory epithelium. The study presents the first attempt to investigate EM in a large series of patients. Our results enrich the available information about the histoepidemiology of prostatic EM. Moreover, EM is more common in a focal lesion, found in small groups of ductal secretory epithelial cells while EM in TURP-specimens is associated with BPH and HP in all the cases.

Keywords: Eosinophilic metaplasia, prostate, prostatitis

How to cite this article:
Koleva MS, Dikov DI, Belovezhdov VT, Sarafian V. Eosinophilic metaplasia in transurethral resection of the prostate. Indian J Pathol Microbiol 2020;63:423-6

How to cite this URL:
Koleva MS, Dikov DI, Belovezhdov VT, Sarafian V. Eosinophilic metaplasia in transurethral resection of the prostate. Indian J Pathol Microbiol [serial online] 2020 [cited 2020 Sep 21];63:423-6. Available from: http://www.ijpmonline.org/text.asp?2020/63/3/423/291678





   Introduction Top


The presence of bright eosinophilic cytoplasmic granules in prostatic epithelium on routine-stained sections is a vaguely recognized morphological phenomenon, which in the early descriptions is known as Paneth cell-like changes (PCLC) or Paneth cell-like metaplasia (PCLM).[1],[2] According to the modern concepts of this prostatic epithelial metaplasia, the terms PCLC or PCLM remain reserved only for prostatic carcinoma (PCa), containing neuroendocrine cells with large eosinophilic granules.[3] According to the most recent definition, the presence of eosinophilic granules with different sizes in the benign prostatic epithelium is termed “eosinophilic metaplasia” (EM).[4],[5] The granules are positive for the periodic acid-Schiff's procedure (PAS) and immunohistochemically for prostate-specific antigen (PSA), α-1-antichymotrypsin, and MUC1 while neuroendocrine markers (chromogranin, synaptophysin, serotonin, and neuron-specific enolase), lysozyme, and S100 protein remain negative.[1],[4],[5]

The frequency of EM is investigated in specimens of prostatic needle biopsies and total prostatectomies.[4] Only single cases of EM in transurethral resection of prostate (TURP)-material have been described until now.[1],[2],[6] No studies on this lesion in large series of TURP-specimens are available so far.

The aim of the current investigation is to examine some histoepidemiological indicators of EM in the patient population from a general hospital, in the context of the basic prostate pathology in TURP-material.


   Materials and Methods Top


A retrospective record review was performed on 61 TURP-specimens for a period of 1 year (2014 year). The study was approved by the hospital ethics committee.

The age of the patients ranged from 54 to 88 years (mean 72.2 years). The leading clinical symptoms covered the so-called prostatic syndrome typical for benign prostatic hyperplasia (BPH), representing a basic indication for surgical intervention. Neither radiation treatment of the genital area nor chemotherapy within the last months before TURP was performed.

All specimens were routinely fixed in 10% buffered formalin and embedded in paraffin for histological evaluation. Tissue sections from 1 to 10 paraffin blocks for each case, stained with hematoxylin-eosin (HE), were examined retrospectively for EM independently by two pathologists.

EM is characterized by the presence of intensely eosinophilic cytoplasmic granules with different sizes (large and small) filling the apical cytoplasm of the benign prostatic secretory epithelium.[4],[5]

The histological distribution of EM is reported as focal when EM is seen in only one field of view and affects a part of one glandular duct or lobule at moderate microscopic magnification (×100). EM is reported as diffuse when it is multifocal and/or affects several adjacent fields of view at the same microscopic magnification. EM may be distributed in single or small groups of cells (<10 cells with eosinophilic granular cytoplasm), and in large groups of cells (>10 cells).

Simultaneously, BPH, National Institutes of Health (NIH)-category IV prostatitis (so-called histologic prostatitis (HP)),[7],[8] and prostatic adenocarcinoma (PCa) were also evaluated.

In 20 cases with EM, standard 4-μm-thick consecutive tissue sections were cut and stained with HE, hematoxylin-phloxine-saffron (HPS), and PAS, to compare the standard histological procedures and the artifact phenomena in TURP's EM.


   Results Top


EM was detected in 34/61 cases (55.7%) localized in the transition zone of the prostate [Figure 1]a. The apical portions of secretory epithelial cells showed either partial or complete EM and were filled with PAS-positive eosinophilic cytoplasmic granules of different sizes, [Figure 1]b and [Figure 1]c.
Figure 1: Eosinophilic metaplasia (EM) of the prostate: (a) EM in ductal secretory epithelium on the right side of the image (arrows). (b) The apical portions of secretory cells show partial or complete EM. (c) The eosinophilic cytoplasmic granules in EM are positive with periodate Schiff's procedure (PAS) ×400. (d) EM is found in ductal (thin arrows) and acinar (thick arrows) structures; moderate to high grade of glandular, periglandular and intesrtitial chronic histologic prostatitis is also present: Hematoxylin-phloxine-saffron, (a) ×200; (b) ×400; (c) serial sections from (1b) ×400; (d) ×200

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Depending on the location, EM was found in glandular structures with predominantly ductal (20/34 cases; 58.8%) or predominantly acinar architecture (8/34 cases; 23.6%). In 6/34 (17.6%) of the cases, both ductal and acinar localization was observed [Figure 1]d and [Figure 2]d. Basal cells were readily apparent or prominent in all involving ducts and acini with EM.
Figure 2: The histological distribution of eosinophilic metaplasia (EM) may by focal (a, thin arrows) and diffuse (b, thick arrows). Benign prostatic hyperplasia (a) and moderate periglandular chronic histologic prostatitis (b) are also observed. EM is found in single or small groups of cells (c) or in large groups of cells in ductal (thin arrows) and acinar (thick arrows) structures (d): Hematoxylin-phloxine-saffron, (a) ×100; b) ×100; (c) ×630; (d) ×200

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The histological distribution of EM was focal in 25/34 cases (73.5%) and diffuse in 9/34 (26.5%) of cases [Figure 2]a and [Figure 2]b]. In 30/34 (88.2%) of cases, EM was found in single or small groups of cells, and in 4/34 (11.8%) in large groups of cells [Figure 2]c and [Figure 2]d. The age of the patients with EM ranged from 54 to 87 years (mean 71.8 years).

BPH was detected in all TURP-cases. HP was identified in 77% of all TURP cases (47/61). Low Gleason grade PCa was found in 4/61 cases but not in association with EM. Both BPH and HP (of moderate-to-high grade with glandular, periglandular and stromal localization) were noted in all cases with EM [Figure 1]d and [Figure 2]b.

The comparative study of both standard histological procedures carried out in 20 cases showed better visualization of EM with HPS than with HE staining (18/20 cases) [Figure 3]a and [Figure 3]b.
Figure 3: Visualization of eosinophilic metaplasia (arrows) with hematoxylin-eosin (a) and hematoxylin-phloxine-saffron (b) staining serial sections: (a) hematoxilin-eosin, ×400; (b) hematoxylin-phloxine-saffron, ×400

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Relatively often (11/20; 55%), in the electrocoagulated periphery of TURP-fragments, secretory glandular cells showed PAS negative pseudoeosinophilic cytoplasm, unlike the real EM [Figure 4].
Figure 4: Secretory glandular cells located in the electrocoagulated periphery of some TURP-fragments show pseudoeosinophilic cytoplasm (a, arrows) which is negative with periodate Schiff's procedure (PAS) (b, arrows), while EM in eosinophilic metaplasia in secretory prostatic epithelium is stained positively with PAS: Serial sections: a) hematoxylin-phloxine-saffron, ×100; (b) PAS × 100

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   Discussion Top


Literature data revealed that the frequency of EM varies from 12% to 23% of prostatic needle biopsies and represents 20% of total prostatectomies.[4] Only single cases of EM in TURP-material have been described so far.[1],[2],[6],[9]

We present herein the first histoepidemiological study of EM in a large series of TURP-specimens. We show an increased frequency of EM in TURP (55.7%.) This observation is twice more common than in prostatic needle biopsies and total prostatectomies.[4] Our quantitative results support the data of other authors,[1] that EM is often a focal lesion (73.5%), found in small groups (88.2%) of secretory epithelial cells of predominantly ductal structures (58.8%).

EM in TURP-specimens is combined with BPH and HP in all of the cases.

The mean age of the patients with EM is 71.8 years, similar to those in previous studies [1] and identical to the patients with HP in our TURP series. Our results confirm the primary hypothesis underlined in the present study that the histopathological study of EM in TURP material is a suitable model for finding a link between EM and two of the most important socially significant prostate diseases: BPH and prostatitis from category IV. In addition, the results obtained by us give new extra information about the frequency of EM and the histological distribution of the process.

The pathogenesis of EM has not been discussed in the scarce literature available on the topic. Our results provide extra data about the pathogenesis and morphogenesis of EM. There is a single observation showing a variable degree of association of EM with chronic inflammation. Our results confirm this relationship.[4],[6],[9],[10] Cheng et al. describe EM as a lesion that is frequently encountered in inflammatory conditions, suggesting a host response to an altered cellular milieu.[4] Gaudin et al. described EM, in benign prostate in 32% of the patients with post-radiation therapy for PCa, in close association with chronic inflammation.[10] We published two case reports revealing the association of chronic prostatic inflammation (nonspecific granulomatous prostatitis) with EM in TURP-material.[6],[9]

The current internationally recognized and worldwide accepted NIH classification of prostatitis syndrome includes four categories: acute and chronic bacterial prostatitis (category I and II); the previously known “nonbacterial chronic prostatitis” which has been divided into two categories respectively: inflammatory (category IIIA) and noninflammatory (category IIIB) chronic prostatitis; and a completely new entity, asymptomatic inflammatory prostatitis (category IV) which has been neglected for a long time in previous classification systems.[7] Category IV prostatitis or histologic prostatitis (HP) is the most frequent inflammation of the prostate in men with no clinical symptoms related to urinary tract infection or pelvic pain.[11] HP is an incidental pathological finding, which appears to be the most common type of prostatic inflammation diagnosed in patients biopsied for prostate cancer screening or operated by TURP for BPH.[12],[13],[14]

The coexistence of EM with both BPH and HP in all of the cases shows that EM is a process that may reflect the morphological status of urinary obstruction due to BPH and to supplementary low or high-grade HP. It could be speculated that the more common localization of EM in prostatic ducts reflects the histological mechanics (compression of BPH-nodules) or/and inflammatory (HP) obstruction. That is why EM is more frequently observed in prostate specimens from TURP with BPH and HP rather than in thin needle biopsies and radical prostatectomies.[4] In a histopathological study of the epididymis, EM (earlier known as PCLC) is interpreted as intracytoplasmic lysosomal accumulation which serves as a microscopic indicator of ductal obstruction.[15]

We assume that the presence of EM in prostate ductal or acinar secretory epithelium in association with HP represents a mechanism of phenotypic cellular adaptation to the changes in the prostate due to persistent active inflammation.[6],[9] This idea is supported by the MUC-1 expression in EM that we reported recently,[5] knowing that the MUC-1 protein plays protective and immunoregulatory functions.[16],[17] The expression of MUC-1 in EM shows that phenotypically modeled secretory cells in EM try to maintain the lumenization of tissue structures in conditions of chronic impairment and inflammation (HP).[5]

In the present investigation, we do not establish an association between EM and PCa.

In addition, in our comparative study of two standard histological techniques, we show for the first time, that better visualization and reproducible interpretation of EM is seen by using the HPS stain. The phloxinophilia and positivity for PAS show that the cytoplasmic granules in EM contain proteins and carbohydrates. Phloxine is used as a component of the basic staining technique (HPS) in the French-speaking countries and is also applied to prove protein-rich zymogenic (exocrine) granules.[18]

During our investigation, in 55% of the cases, we found ductal or acinar benign glandular structures with cytoplasmic eosinophilia located in the electrocoagulated periphery of resected TURP-fragments. The negativity of these cells for PAS, unlike secretory cells with EM, shows that this cytoplasmic pseudoeosinophilia is an artifact caused by the electrocoagulation during TURP-surgical procedure. Obviously, when reporting the EM lesion in TURP-specimens, such areas should not be considered. The strengths of the present study are the complement of histopathology, pathogenesis, and differential diagnosis of EM. The limitations of the present study include the lack of data about the serum level of PSA and the weights of TURP-specimens. This, in turn, limits, although insignificantly, the complexity of the clinicopathological correlations of the data presented.

Further investigations of large series of patients with different types of prostate materials (autopsies, fine needle biopsies, adenomectomies, and TURP) with statistical data processing is necessary to make a more detailed characterization of the close relationships of EM, HP, and BPH.

In conclusion, we report the first quantitative study of EM in TURP-material. Our investigation presents a histo epidemiological analysis of EM in relation and correlation to the basic prostate pathology in TURP-specimens: BPH and NIH-category IV prostatitis (HP).

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

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Weaver M, Abdul-Karim F, Srigley J, Bostwick D, Ro J, Ayala A. Paneth cell-like change of the prostate gland. A histological, immunohistochemical, and electron microscopic study. Am J Surg Pathol 1992;16:62-8.  Back to cited text no. 1
    
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Frydman CP, Bleiweiss IJ, Under PD, Gordon RE, Brazenas NV. Paneth cell-like metaplasia of the prostate gland. Arch Pathol Lab Med 1992;116:274-6.  Back to cited text no. 2
    
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Ablakha H, Bostwick DG. Paneth cell-like changes in prostatic adenocarcinoma represent neuroendocrine differentiation: Report of 30 cases. Hum Pathol 1994;25:135-9.  Back to cited text no. 3
    
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Cheng L, MacLennan GT, Abdul-Karim FW, Lopez-Beltran A, Montironi R. Eosinophilic metaplasia of the prostate: A newly described lesion distinct from other eosinophilic changes in prostatic epithelium. Anal Quant Cytol Histol 2008;30:226-30.  Back to cited text no. 4
    
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Dikov D, Vassilev I, Dimitrakov J. Nonspecific granulomatous prostatitis with calculous ductal ectasia and extensive Paneth cell-like epithelial metaplasia. Case report. APMIS 2005;113:564-7.  Back to cited text no. 6
    
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Krieger JN, Nyberg L, Nickel JC. NIH consensus definition and classification of prostatitis. JAMA 1999;282:236-7.  Back to cited text no. 7
    
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Dikov D, Koleva M, Peshev J, Belovejdov V. Nonspecific granulomatous prostatitis in association with eosinophilic epithelial metaplasia and prostatic adenocarcinoma: A case report. Indian J Pathol Microbiol 2017;60:409-11.  Back to cited text no. 9
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10.
Gaudin PB, Zelefsky MJ, Leibel SA, Fuks Z, Reuter VE. Histopathologic effects of free-dimensional conformal external beam radiation therapy on benign and malignant prostate tissue. Am J Surg Pathol 1999;23:1021-31.  Back to cited text no. 10
    
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Gurel B, Lucia MS, Thompson IM Jr, Goodman PJ, Tangen CM, Kristal AR, et al. Chronic inflammation in benign prostate tissue is associated with high-grade prostate cancer in the placebo arm of the prostate cancer prevention trial. Cancer Epidemiol Biomarkers Prev 2014;23:847-56.  Back to cited text no. 12
    
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Sfanos KS, Hempel HA, De Marzo AM. The role of inflammation in prostate cancer. Adv Exp Med Biol 2014;816:153-81.  Back to cited text no. 13
    
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Robert G, Descazeaud A, Nicolaiew N, Terry S, Sirab N, Vacherot F, et al. A inflammation in benign prostatic hyperplasia: A 282 patients' immunohistochemical analysis. Prostate 2009;69:1774-80.  Back to cited text no. 14
    
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Shah VI, Ro JY, Amin MB, Mullick S, Nazeer T, Ayala AG. Histologic variations in the epididymis: Findings in 167 orchiectomy specimens. Am J Surg Pathol 1998;22:990-6.  Back to cited text no. 15
    
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Kato K, Lillehoj EP, Lu W, Kim KC. MUC1: The first respiratory mucin with an anti-inflammatory function. J Clin Med 2017;29;6:110.  Back to cited text no. 16
    
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Dhar P, McAuley J. The role of the cell surface mucin MUC1 as a barrier to infection and regulator of inflammation. Front Cell Infect Microbiol 2019;24;9:117.  Back to cited text no. 17
    
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Doglioni C, Laurino L, Dei Tos AP, De Boni M, Franzin G, Braidotti P, et al. Pancreatic (acinar) metaplasia of the gastric mucosa. Histology, ultrastructure, immunocytochemistry, and clinicopathologic correlations of 101 cases. Am J Surg Pathol 1993;17:1134-43.  Back to cited text no. 18
    

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Correspondence Address:
Maria S Koleva
Department of General and Clinical Pathology, Medical University – Plovdiv, Bul., Vasil Aprilov” 15A, 4002 Tsentar, Plovdiv
Bulgaria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJPM.IJPM_593_19

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