Adenosis
One of the most common lesions that may be confused with carcinoma is adenosis (atypical adenomatous hyperplasia) [1, 2, 3] . There is a wide spectrum in the literature in terms of the reported incidence of adenosis on TURP, ranging from 2.2% to 19.6% [4, 5] . The reason for this broad range is different thresholds for diagnosing a focus of crowded glands as adenosis. Included within the lower threshold are prostate specimens with foci of crowded glands, which could be considered a minimal example of adenosis, although they do not closely mimic adenocarcinoma. At the other extreme, seen in 1.6% of benign TURPs performed at The Johns Hopkins Hospital, adenosis closely mimics adenocarcinoma of the prostate. As adenosis preferentially occurs within the transition zone, it is more frequently seen on TURP than on needle biopsy, where it is seen in approximately 0.8% of cases. Adenosis is often multifocal.

The distinction of adenosis from low-grade adenocarcinoma is based on architectural and cytologic features (Table 2).

Table 2: Diagnostic Criteria For Adenosis

Adenosis	Low Grade Carcinoma
Features Seen at Low and Intermediate Magnification
Lobular growth	May be infiltrative/haphazard
Small crowded glands admixed with larger glands	May be pure population of small crowded glands
Features Seen At High Magnification
Huge (>3 micron) nucleoli absent	Occasionally huge nucleoli present
Small glands share cytoplasmic and nuclear features with admixed larger benign glands	Small glands differ from surrounding benign glands in cytoplasmic and/or nuclear features
Pale-clear cytoplasm	May have amphophilic cytoplasm
Blue-tinged mucinous secretions Rare	Blue-tinged mucinous secretions common
Corpora amylacea common	Corpora amylacea rare
Occasional glands with basal cells	Basal cells absent
Basal cell-specific anti-keratinantibodies label basal cells in some small glands	Small glands are not immunoreactive with basal cell-specific anti-keratin antibodies

In order to minimize misdiagnoses, the constellation of histologic features seen in a lesion should outweigh the significance of any one diagnostic feature. At scanning magnification, adenosis is characterized by a lobular proliferation of small glands. In contrast, low grade carcinoma has a haphazard, irregular, infiltrative growth pattern. Despite the overall lobular pattern seen in adenosis, 19% of cases reveal minimal infiltration of glands into the surrounding stroma.

Probably the most important differentiating feature of adenosis seen on H&E stain is that within a nodule of adenosis there are elongated glands with papillary infolding and branching lumina typical of more benign glands, yet in their nuclear and cytoplasmic features they look similar to the adjacent small glands suspicious for carcinoma. Glands of adenocarcinoma, even in the unusual case when the tumor is fairly lobular, shows a pure population of small crowded glands without benign architectural features that do not merge in with adjacent larger benign glands.

At higher power, adenosis is typically composed of small glands with pale to clear cytoplasm, as opposed to some carcinomas, which have more amphophilic cytoplasm. Occasional single cells or poorly formed glands are not uncommon in a nodule of adenosis and probably represent tangential sections of small glands (Table 3).

Table 3: Nondiagnostic Features In Adenosis And Carcinoma

Features Shared in Adenosis and Cancer

Crowded (back-to-back glands) Intraluminal crystalloids Medium-sized (<3 microns) nucleoli Scattered poorly formed glands and single cells Minimal infiltration at periphery of nodule

Although adenosis typically has bland appearing nuclei without nucleoli, in 40% of cases, fairly prominent nucleoli are present, which should not lead to the diagnosis of carcinoma [6]. Thirty per cent of low-grade carcinomas also have either no prominent or at most rare prominent nucleoli. These findings emphasize that, although nucleoli are generally helpful in differentiating adenosis from adenocarcinoma, there is overlap between the two entities.

The luminal contents also may be useful in this differential diagnosis. Corpora amylacea are commonly seen in adenosis, and are rare in carcinoma. Only 2% of cases of adenosis contain blue intraluminal secretions visible on hematoxylin and eosin-stained sections, a feature common in low-grade carcinomas. It is not helpful to perform special stains for mucin. Despite earlier studies' claims that acid mucin was diagnostic of carcinoma, a later work found that 54% of foci of adenosis contained acid mucin secretions [7].

Crystalloids are intraluminal structures that have been touted as distinguishing adenosis from carcinoma. However, 18% to 39% of foci of adenosis contain crystalloids, sometimes in great number. Crystalloids should not be used to differentiate adenosis and carcinoma (Table 3).

The presence of basal cells is the one feature seen in adenosis that is typically not seen in carcinoma. Although basal cells may be difficult to identify within many of the glands, a flattened basal cell layer can be seen in at least some of the glands. As long as the glands with a basal cell layer are otherwise identical to the glands where a basal cell layer can not be identified, then the entire lesion is benign. It is important to distinguish basal cells from adjacent fibroblasts. While fibroblasts have elongated pointed hyperchromatic nuclei, basal cell nuclei that are recognizable in routine sections have a more cigar-shaped ovoid contour with chromatin similar to that of the overlying secretory cells. In foci of glandular crowding where all of the features are typical of adenosis and there is no cytologic atypia, adenosis can be diagnosed without immunohistochemical stains even if basal cells are not visible on routine sections.

In cases where the architectural pattern favors adenosis yet there are visible nucleoli, the diagnosis can be clarified using immunohistochemistry for basal cells. The use of a basal cell specific antibody to high molecular weight keratin is helpful since some glands (even though maybe only a minority) will show a thin rim of patchy keratin immunoreactivity beneath the cuboidal or columnar secretory cells [1, 2, 8] . On needle biopsy, due to the limited number of glands in question, basal cell specific antibodies must be interpreted with caution. Because basal cell staining may be patchy in adenosis, negative staining in a small focus of glands is not necessarily indicative of malignancy. However, if some of the glands within a crowded glandular focus on needle biopsy demonstrate a basal cell layer, then adenosis can be diagnosed.

Although adenosis mimics carcinoma, there is no conclusive evidence suggesting that patients with adenosis have an increased risk of harboring or developing adenocarcinoma of the prostate [9, 10, 11] . When diagnosing adenosis, we include the following statement, "Adenosis, although mimicking cancer, has not been shown to be associated with an increased risk of prostate cancer".

Atrophy
Atrophy is best diagnosed at medium to low magnification. Although the glands may appear infiltrative, they appear invasive as a patch not as individual glands infiltrating in between larger benign glands. At low power, atrophic glands have a very basophilic appearance. This basophilic appearance is due to their scant cytoplasm and crowded nuclei such that at low magnification one is merely seeing a nuclear outline of the gland. Longitudinal tangential sections of atrophic glands results in cords of cells that can further mimic cancer. In some cases there may be associated fibrosis, which gives the atrophic glands a more infiltrative appearance that has been termed sclerotic atrophy. A characteristic finding in some cases is the presence of a centrally dilated atrophic gland surrounding by fibrosis and clustered smaller glands, which has been termed "post-atrophic hyperplasia (PAH]" [12]. Compared to atrophy, gland-forming adenocarcinomas of the prostate typically have a greater amount of cytoplasm so that at low magnification the neoplastic glands are not as basophilic. Atrophy may show enlarged nuclei and prominent nucleoli, although not the huge eosinophilic nucleoli seen in some prostate cancers. Although prominent nucleoli are more common in atrophic glands associated with inflammation, we have also seen prominent nucleoli in atrophy without inflammation. Furthermore, the inflammation associated with atrophy may be trivial and chronic in nature but still give rise to significant nuclear atypia. In deciding whether an atypical focus represents carcinoma, the presence of atrophic cytoplasm should, in general, dissuade one from diagnosing carcinoma. When there are concerns as to whether a focus represents atrophy or adenocarcinoma, immunohistochemistry with antibodies to high molecular weight cytokeratin can be performed to resolve the issue. Atrophy uniformly labels with high molecular weight keratin in contrast to negative staining in adenocarcinoma.

Rarely, carcinoma with an atrophic appearance may be present on needle biopsy. The diagnosis of carcinoma in these cases is made on: 1) a truly infiltrative process with individual small atrophic glands situated between larger benign glands; 2) the concomitant presence of ordinary less atrophic carcinoma; and 3) greater cytologic atypia than is seen in benign atrophy.

A variant of atrophy that may cause confusion with carcinoma is "partial atrophy" [13]. Partial atrophy may still retain the lobular pattern of atrophy or have more of a disorganized diffuse appearance. Partial atrophy lacks the basophilic appearance of fully developed atrophy as the nuclei are more spaced apart. The presence of crowded glands with pale cytoplasm may lead to an overdiagnosis of low-grade adenocarcinoma. At higher power, however, the glands have benign features characterized by undulating luminal surfaces with papillary infolding. Most carcinomas have more straight, even luminal borders. In addition, the glands are partially atrophic with nuclei in areas reaching the full height of the cytoplasm. The nuclear features in partial atrophy tend to be relatively benign without prominent nucleoli. One should hesitate diagnosing cancer when the nuclei occupy almost the full cell height and the cytoplasm has the same appearance as surrounding more obvious benign glands.

Basal Cell Hyperplasia
The most common form of basal cell hyperplasia consists of tubules or glands with piling up of the basal cell layer [14, 15, 16] . In some cases of florid basal cell hyperplasia the basal cell proliferation still retains a lobular configuration. In other instances the lobular configuration may either be lost or not appreciated because of the fragmented nature of the transurethral resection specimen. At low magnification, basal cell hyperplasia can be distinguished from carcinoma by its very basaloid appearance due to multilayering of the basal cells which have scant cytoplasm. Within basal cell hyperplasia, there is piling up of the nuclei within the lumen ranging from a single cell layer in a few glands, to 3 to 4 cells thick in other glands, to solid nests of epithelium. Basal cell hyperplasia may reveal focal cribriform glands. Cribriform basal cell hyperplasia in most cases resembles back-to-back glands of basal cell hyperplasia rather than true cribriform glands. Adjacent to cribriform basal cell hyperplasia are usually more typical individual glands of basal cell hyperplasia. Basal cell hyperplasia is also one of the few prostatic entities that contain well-formed lamellar calcifications. Another unique feature seen within the cells of basal cell hyperplasia is the presence of intracytoplasmic eosinophilic globules. Basal cell lesions are preferentially located in the transition zone and are seen on TURP, although occasionally, we have seen basal cell hyperplasia on needle biopsy.

If by light microscopy there is difficulty in distinguishing basal cell hyperplasia from prostatic adenocarcinoma, positive staining with immunohistochemistry for basal cell specific antibodies can identify the lesion as benign [17, 18] . Basal cell hyperplasia may have prominent nucleoli, but is otherwise identical to ordinary basal cell hyperplasia.Basal cell hyperplasia with prominent nucleoli is distinguished from adenocarcinoma by the multilayering of its nuclei, solid nests, and atrophic cytoplasm. There is no known association between basal cell hyperplasia showing prominent nucleoli and either acinar adenocarcinoma or basaloid carcinoma.

Colonic Mucosa
Rarely, distorted fragments of colonic mucosa on transrectal biopsies of the prostate can be confused with adenocarcinoma of the prostate. Features that can mimic prostate cancer are the presence of luminal blue-tinged mucinous secretions and reactive/reparative atypia. The presence of goblet cells and other features of colonic tissue, such as a potentially thickened basement membrane, lamina propria, and muscularis should prevent a misdiagnosis. Immunohistochemistry with prostatic markers can verify the nonprostatic nature of the lesion.

Cowper's Glands
Cowper's glands can be seen on transurethral resection or on needle biopsy as a potential pitfall in the diagnosis of prostate cancer [19, 20] . The diagnosis of Cowper's glands rests on the recognition of a noninfiltrative lobular pattern of a dimorphic population of ducts and mucinous acini in Cowper's glands. The presence of abundant mucin-filled cytoplasm also distinguishes this lesion from carcinoma. Although prostate cancer cytoplasm may contain neutral mucinous secretions, prostate cancers lack abundant mucinous cytoplasm to the extent that the lumina are almost occluded. Foamy gland carcinomas have almost as abundant cytoplasm, yet in foamy gland cancer the glands are larger and mucin stains are negative.

In difficult cases where ducts in Cowper's glands may not be obvious, immunohistochemistry with a panel of antibodies may be useful. In our study, prostate specific acid phosphatase (PSAP) was negative in all cases, although the abundant cytoplasm of the acinar cells decorated focally with PSA in a heterogeneous "clumped" fashion in four of ten cases. In contrast to prostate cancer, high molecular weight cytokeratin (34BE12) stain the ductal epithelium, hybrid cells, and an attenuated basal layer at the periphery of acini.

Mesonephric Hyperplasia
Identical to the lesion seen in the female genital tract, mesonephric hyperplasia has rarely been seen in the prostate on either TURP or in radical prostatectomy specimens [21]. It is distinguished from carcinoma by the atrophic appearance of the glands, occasional papillary tufting, lack of stromal reaction, dense colloid secretions, and negative immunoreactivity for PSA and PSAP.

Nephrogenic Adenoma
Nephrogenic adenomas appear as papillary, polypoid, hyperplastic, fungating, friable, or velvety lesions. Typically found in the bladder, 12% are seen in the urethra. Most nephrogenic adenomas measure less than 1 cm., although they may attain dimensions as large as 7 cm. In eighteen percent of cases, multiple lesions are identified. Lesions occurring in the prostatic urethra may be confused with adenocarcinoma of the prostate [22, 23] .

Nephrogenic adenomas have a broad histologic spectrum. Proliferations of small solid to hollow tubules, lined by low columnar to cuboidal epithelial cells with eosinophilic to clear cytoplasm, are identified in the majority of cases. Vascular-like structures with attenuated epithelium, with or without hobnail nuclei, are the second most common pattern. Verification that these vascular-like structures are epithelial can be accomplished with immunohistochemistry for cytokeratin, which can help establish the correct diagnosis. Cords and individual cells with cuboidal, eosinophilic to clear cytoplasm, polypoid or papillary configurations, and rare signet ring cell-like structures are identified in a decreasing percent of cases. A distinguishing feature of nephrogenic adenoma is the presence of a thickened hyaline sheath around some of the tubules, which may be enhanced with periodic acid Schiff (PAS) stains. Cystic tubules may contain thyroid-like eosinophilic secretions Most cases of nephrogenic adenoma are comprised of multiple histologic patterns.

Nuclear atypia, when present, appears degenerative and mitoses are either absent or rare. Nuclei are enlarged and hyperchromatic, yet have a smudged indistinct chromatin pattern. These atypical nuclei often reside in cells with an endothelial or hobnail appearance lining vascular-like dilated tubules. The presence of prominent nucleoli in many cases examined is also a source of possible confusion with prostate cancer. However, prominent nucleoli are usually only focally present within a lesion, and often seen in association with degenerative nuclear atypia or with other features not commonly seen in prostate cancer, such as hobnail-like cells or peritubular hyaline sheaths. Another possible source of confusion with a malignant lesion of the prostate is the presence of blue-tinged mucinous secretions within tubular lumina. Further mimicking prostate cancer is that in the majority of cases of nephrogenic adenoma arising from the prostatic urethra some degree of muscle involvement is present [22]. Features helpful to distinguish these cases of nephrogenic adenoma from prostate cancer include the presence of more typical nephrogenic adenoma architectural patterns in other areas of the lesion and that the lesion is located immediately below the urothelial lining, a site unusual for prostate cancer. The presence of an acute and/or chronic inflammatory infiltrate around and within tubular lumina of nephrogenic adenoma structures is also not a feature of most prostate cancers.

Cytoplasmic staining for 34BE12 is found in more than one half the cases of nephrogenic adenoma, in contrast to negative labeling in prostate cancer. Focal cytoplasmic staining and/or positive tubular secretions for PSA and PSAP may be seen in almost half of nephrogenic adenomas, although the staining is not as intense as typically seen in moderately-differentiated adenocarcinomas of the prostate [22].

Radiation Atypia
The distinction between irradiated non-neoplastic prostatic glands and carcinoma is best made on the low magnification architectural pattern of the glands [24, 26] . Within the radiated normal prostate, glands maintain their normal architectural lobular configuration. In contrast to carcinoma, the non-neoplastic glands are separated by a modest amount of prostatic stroma. On higher magnification, whereas glands of prostatic carcinoma are lined by a single cell layer, there is piling up of the nuclei within irradiated normal prostate as well as an occasional recognizable basal cell layer. This piling up of the cells in radiated benign glands frequently appears slightly spindled resembling transitional cell metaplasia. The finding of scattered markedly atypical nuclei within well-formed acini is typical of radiated benign glands and rare in prostate carcinoma. Prostate carcinomas that are sufficiently differentiated to form glands rarely manifest the degree of atypia seen with radiation, and if present would be more uniformly present in all cells. Radiated nuclei also have a degenerative, hyperchromatic smudgy appearance as opposed to malignant prostatic nuclei that usually contain prominent nucleoli. Irradiated non-neoplastic glands often are atrophic, in contrast to gland forming prostatic adenocarcinomas that typically have abundant cytoplasm. It has been demonstrated that high molecular weight cytokeratin immunohistochemistry can aid in the diagnosis of irradiated prostate by identifying basal cells within benign radiated glands [25].

Seminal Vesicles
The recognition of seminal vesicle rests on appreciating its architectural as well as cytologic features. Seminal vesicles are characterized by a central large dilated lumina with numerous small glands clustered around the periphery. Often the glands appear to bud off from the central lumen. Although on needle biopsy it may be difficult to recognize the architectural pattern of seminal vesicles due to the limited tissue, certain features may be present. A common finding on needle biopsy of the seminal vesicle is the dilated irregular lumen of the seminal vesicle seen at the edge of the tissue core, where the core has fragmented as it entered the seminal vesicle lumen. Surrounding this dilated structure are clusters of smaller glands. Recognition that the small glands suspicious for carcinoma are all clustered around this dilated glandular structure is the first step in not overdiagnosing seminal vesicle epithelium as carcinoma. Verification that one is dealing with seminal vesicle epithelium can readily be accomplished at higher magnification examination. Seminal vesicle epithelium characteristically have scattered cells showing prominent nuclear atypia [27, 28, 29, 30] . These nuclei are markedly enlarged with bizarre shapes and have marked hyperchromasia that often obscures nuclear details. Despite these pleomorphic features, these nuclei lack mitotic activity. The atypia appears degenerative in nature, similar to that which is seen with radiation atypia. The common finding within seminal vesicles of markedly atypical nuclei present within well-formed glandular structures differs from prostate cancer in which gland forming well to moderately-differentiated carcinomas have only slight to moderate nuclear atypia. Even in poorly-differentiated prostatic carcinoma that lacks glandular differentiation, one rarely sees the severe atypia that is present within scattered seminal vesicle epithelial cells. Prominent globular golden brown lipofuscin granules are typical of seminal vesicle epithelium. Benign prostate tissue, high grade PIN, and rarely carcinoma may contain lipofuscin pigment, but it differs in that the granules are smaller and more red-orange or blue [31]. If there still exists questions as to whether the lesion is seminal vesicle epithelium or prostatic adenocarcinoma, immunohistochemistry for high molecular weight cytokeratin will label basal cells surrounding seminal vesicle epithelium, whereas basal cells are absent in prostate adenocarcinoma. Caution must be used with immunohistochemistry using polyclonal antibodies to PSA as it will label seminal vesicle tissue; monoclonal antibodies to PSA does not exhibit this cross-reactivity [32].

Verumontanum Mucosal Gland Hyperplasia (VMGH)
The verumontanum is situated along the posterior prostatic urethral wall and is the point at which the utricle and ejaculatory ducts merge with the prostatic urethra. The small size and crowded nature of verumontanum mucosal glands may simulate low-grade prostatic adenocarcinoma [33, 34] . The glands of VMGH lack the infiltrative and haphazard arrangement of the glands typically found in prostatic adenocarcinoma. In addition, VMGH is characteristically identified adjacent to and often contiguous with urothelium. Contents of these mucosal glands are sufficiently distinct to allow discrimination from prostatic adenocarcinoma. Unlike prostatic adenocarcinoma, corpora amylacea are a feature typical of VMGH. Also, in VMGH one characteristically finds distinctive brown-orange concretions. Verumontanum mucosal glands are immunophenotypically similar to prostatic acini; thus, the secretory cells of these mucosal glands stain positively with antibodies to prostate-specific antigen (PSA), whereas the basal cells stain with antibodies to high molecular weight cytokeratin.

Table 4. Mimickers of Gleason Score 7-10 Adenocarcinoma

Entity	Predominant Mode of Sampling
Nonspecific granulomatous prostatitis	TURP = Needle
Paraganglia	TURP > Needle
Clear cell cribriform hyperplasia	TURP > Needle
Sclerosing adenosis	TURP >> Needle
Xanthoma	Needle > TURP
Signet ring cell lymphocytes	TURP

Clear Cell Cribriform Hyperplasia
Clear cell cribriform hyperplasia occurs within the transition zone and is mostly seen in TURP specimens removed for urinary obstructive symptoms, and rarely seen on needle biopsy. Although it is considered by some to be a cribriform variant of BPH, it remains useful from the practical standpoint to consider it as a distinct entity, as it may be confused with either prostatic intraepithelial neoplasia (PIN) or adenocarcinoma of the prostate [35].

In florid cases, cribriform infiltrate the stroma diffusely mimicking cribriform Gleason score 4+4=8 adenocarcinoma. The epithelial cells have distinctive clear cytoplasm and small bland nuclei with inconspicuous or small nucleoli. Around many of the glands of clear cell cribriform hyperplasia is a strikingly prominent basal cell layer, consisting of a row of cuboidal darkly staining cells beneath the clear cells. The basal cell layer may be incomplete and in some glands may be invisible in routine sections. Tangential sections can also result in the appearance of occasional nests of clear cells without cribriform architecture or basal cells. Although usually unnecessary, immunostains for high molecular weight cytokeratin can highlight the basal cell layer [36]. The presence of basal cells around some of the glands in clear cell cribriform hyperplasia rules out carcinoma, even though some glands with identical nuclear and cytoplasmic features may not have an apparent basal cell layer. The glands in clear cell cribriform hyperplasia lack cytologic atypia, in contrast to infiltrating cribriform carcinoma. Also it is uncommon to see cribriform carcinoma unaccompanied by small infiltrating neoplastic glands.

Nonspecific Granulomatous Prostatitis (NSGP)
One of the principle entities that can be confused with high grade prostate cancer is non-specific granulomatous prostatitis [37]. NSGP can closely mimic cancer clinically. In a series of cases on needle biopsy, prostatic carcinoma was suspected or considered prior to biopsy in 55% of cases [38]. Prostate-specific antigen levels greater than 4 ng/nL were seen in 84% of NSGP and digital rectal exam was frequently abnormal.

Although most cases of NSGP seen on needle biopsy do not histologically resemble prostate cancer, 4% of cases can closely resemble cancer. These cases of NSGP consists of sheets of epithelioid histiocytes some with prominent nucleoli with abundant granular cytoplasm.The key feature to avoid a misdiagnosis of cancer is to recognize the other inflammatory cells in nonspecific granulomatous prostatitis, such as scattered neutrophils, lymphocytes, plasma cells, and eosinophils. The presence of scattered multinucleated giant cells may also aid in the diagnosis of NSGP. However, despite its name, approximately 50% of cases of NSGP lack multinucleated giant cells on needle biopsy [38]. In contrast, most adenocarcinomas of the prostate lack an associated inflammatory component [39]. Although it may be difficult to appreciate on needle biopsy specimens, NSGP initially is localized around ruptured ducts and acini.

If there are difficulties in distinguishing NSGP from poorly differentiated adenocarcinoma, immunohistochemistry can be utilized. These epithelioid cells will be negative for PSA, PSAP, and pancytokeratin, and positive for various histiocytic markers [40].

Paraganglia
Paraganglia have been identified in 8% of radical prostatectomies [41]. They are usually present in the posterolateral soft tissue exterior to the prostate. Uncommonly they may be found in the lateral prostatic stroma or in the bladder neck smooth muscle. Rarely paraganglia may be seen on TURP or on needle biopsy where their distinction from carcinoma must be made [42]. They consist of clusters of clear or amphophilic cells with fine cytoplasmic granules and a prominent vascular pattern, often intimately related to nerves. Nucleoli are not prominent, and if nuclear atypia is present it is degenerative in appearance as seen in endocrine lesions. Paraganglia are situated in smooth muscle, not admixed with benign prostate glands. Although this lesion closely mimics high grade adenocarcinoma of the prostate, the highly vascular setting along with the degenerative atypia are clues to prevent a misdiagnosis. Also before diagnosing a small focus of high grade carcinoma on TURP or needle biopsy, where the atypical focus appears entirely extraprostatic, paraganglia should be considered in the differential diagnosis. Verification of the diagnosis can be accomplished with positive immunostaining for neuroendocrine markers and S100, and negative reactivity for PSA and PSAP.

Sclerosing Adenosis
Sclerosing adenosis is found in approximately 2% of prostatic specimens [43, 44, 45] . In most cases, the lesions are discovered incidentally in transurethral resections performed for urinary obstructive symptoms. Usually only one or two small foci are present. Very rarely sclerosing adenosis may be seen on needle biopsy. Sclerosing adenosis consists of a mixture of well-formed glands, single cells, and a cellular spindle cell component. There are several features that should prevent a misdiagnosis of malignancy.

1. Adenocarcinomas of the prostate composed of an admixture of glands, poorly formed glandular structures, and single cells would be assigned a high Gleason score (7 or 8). Prostatic adenocarcinomas with these scores are only rarely seen as limited foci within a TURP. The finding of only one or several small foci of a cellular lesion suspicious for high grade carcinoma should prompt a consideration of sclerosing adenosis or paraganglia. Furthermore, although sclerosing adenosis may be minimally infiltrative at its perimeter, the lesion is still relatively circumscribed in contrast to high grade prostate adenocarcinoma.
2. The glandular structures in sclerosing adenosis resemble those seen in ordinary adenosis. They are composed of cells with pale to clear cytoplasm and relatively benign appearing nuclei. In many of the glandular structures, a basal cell layer can be identified on hematoxylin and eosin stained sections. This contrasts to carcinoma, where basal cells are absent.
3. Sclerosing adenosis contains a dense spindle cell component that is typically lacking in adenocarcinomas. Usually, adenocarcinomas of the prostate show no apparent stromal response or at most a hypocellular fibrotic reaction.
4. A rather unique feature of sclerosing adenosis is the presence of a hyaline sheath-like structure around some of the glands. The glands in ordinary adenocarcinoma lack such a collarette and have a "naked" appearance as they infiltrate the stroma.
5. The relatively bland cytology may also help in distinguishing sclerosing adenosis from adenocarcinoma, although some nuclei within sclerosing adenosis may be moderately enlarged and contain prominent nucleoli.

Signet Ring Lymphocytes
TURP specimens may frequently show aggregates of degenerated lymphocytes with a signet ring cell appearance [46]. This finding results from thermal injury and is not seen in needle biopsy or open prostatectomy specimens. Only rarely are these changes so prominent to be confused with signet ring cell carcinoma.

Xanthoma
Although rare, prostatic xanthoma can be a source of diagnostic confusion, particularly with small tissue fragments such as those obtained from needle biopsies [47]. Features that aid in the recognition of xanthoma include circumscription, clustering of uniform cells that lack gland formation, vacuolated cytoplasm, and benign-appearing nuclei without prominent nucleoli; immunohistochemical studies for histiocytic markers are confirmatory.

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