Pseudohyperplastic Adenocarcinoma Research Articles

Prostatic adenocarcinoma with a peculiar morphology \u2013 a rare case of pseudohyperplastic variant with inverted polarity

BackgroundThe inverted (hobnail) variant of high-grade prostatic intraepithelial neoplasia (HGPIN) has been reported in two previous series and one case of inverted polarity in invasive adenocarcinoma has been reported. We reported an additional case of invasive carcinoma with this peculiar morphology.Case presentationWe reported an additional case of invasive carcinoma with this peculiar morphology. A prostatectomy specimen of a 64-year-old patient showed a GG2 adenocarcinoma with extensive intraprostatic perineural infiltration and extraprostatic extension. Half of the entire tumor showed a distinctive inverted morphology.ConclusionAlthough pseudohyperplastic adenocarcinoma is believed to be a low-grade tumor to be graded as Gleason pattern 3, awareness of this morphology is important to collect more information on its biologic behavior and clinical implication.

Variants of acinar adenocarcinoma of the prostate mimicking benign conditions

Histological variants of acinar adenocarcinoma of the prostate may be of significance due to difficulty in diagnosis or due to differences in prognosis compared to usual acinar adenocarcinoma. The 2016 World Health Organization classification of acinar adenocarcinoma includes four variants that are deceptively benign in histological appearance, such that a misdiagnosis of a benign condition may be made. These four variants are atrophic pattern adenocarcinoma, pseudohyperplastic adenocarcinoma, microcystic adenocarcinoma, and foamy gland adenocarcinoma. They differ from usual small acinar adenocarcinoma in architectural glandular structure and/or cytoplasmic and nuclear alterations. The variants are often admixed, in variable proportions, with usual small acinar adenocarcinoma that is often Gleason pattern 3 but may be high-grade pattern 4 in a minority of cases. Atrophic pattern adenocarcinoma can be identified in a sporadic setting or after radiation or hormonal therapy. This variant is characterized by cytoplasmic volume loss and can resemble benign glandular atrophy, an extremely common benign process in the prostate. The glands of pseudohyperplastic adenocarcinoma simulate usual epithelial hyperplasia, with gland complexity that is not typical of small acinar adenocarcinoma. These complex growth configurations include papillary infoldings, luminal undulations, and branching. Microcystic adenocarcinoma is characterized by cystic dilation of prostatic glands to a size that is much more commonly observed in cystic change in benign prostatic glands. Finally, the cells in foamy gland adenocarcinoma display cytoplasmic vacuolization and nuclear pyknosis, features that can found in benign glands and macrophages. Three of the four variants (atrophic, pseudohyperplastic, and microcystic) are assigned low-grade Gleason pattern 3. Of significance, foamy gland adenocarcinoma can be Gleason pattern 3 but can also be high-grade pattern 4 or 5. Diagnostic awareness of the existence of these deceptively benign-appearing variants of acinar adenocarcinoma is essential so that an accurate diagnosis of prostate cancer may be rendered.

Minimal (Limited) Pseudohyperplastic Prostatic Adenocarcinoma in Needle Prostatic Biopsy.

Study of minimum adenocarcinoma has been done almost exclusively on conventional acinar adenocarcinoma. Pseudohyperplastic adenocarcinoma can be confused with benign lesions because of its well-differentiated appearance and has not been studied when the biopsy shows few malignant glands (limited carcinoma). We reviewed 94 pseudohyperplastic adenocarcinomas diagnosed in prostatic biopsies for a period of 12 years and selected those measuring less than 1 mm or involving less than 5% of the biopsied tissue. We also reviewed 200 consecutive consultations. Four (4.2%) of the 94 cases were limited pseudohyperplastic adenocarcinomas, and 3 were from consultations. Three of them were mistaken for hyperplastic nodules, prostatic adenosis, or prostatic intraepithelial neoplasm. The number of glands varied between 6 and 50 (average 23). Three nodular histological patterns were identified-nodular, adenosis-like, and pseudohyperplastic carcinoma resembling prostatic intraepithelial neoplasia. The diagnosis of adenocarcinoma was not related to the number of neoplastic glands. Histological criteria that were useful included: crowded medium to large glands, papillary infoldings, branching glands, straight luminal borders, hyperchromatic nuclei, nucleomegaly, and apparent nucleoli. Areas of transition to conventional acinar adenocarcinoma were useful in recognizing four of these neoplasms, but were barely apparent in 2 of them. Hyperchromatic nuclei were found in all cases, whereas apparent nucleoli and nucleomegaly were only present in 4. The architectural and cytological criteria for limited acinar adenocarcinoma are only partially useful in interpreting minimum pseudohyperplastic adenocarcinomas. Knowledge of the criteria for malignancy in both neoplasms is important in order to avoid underdiagnosis of malignancy.

Pseudohyperplastic Adenocarcinoma With Foamy Changes in Needle Prostate Biopsy and Prostatectomy.

Pseudohyperplastic adenocarcinoma (PHA) with foamy changes is composed of neoplastic glands that show a cytoarchitectural combination of both neoplasms. However, none of the previously reported cases have shown typical areas of foamy or PHA. We report on the clinicopathological characteristics of 5 cases consisting predominantly of pseudohyperplastic and foamy adenocarcinomas. In several histological fields, this neoplasm mimicked hyperplastic nodules or prostatic adenosis because they showed the nodular pattern of the PHA and the inconspicuous cytological atypia of foamy gland carcinoma. Four cases had a Gleason score of 6. In the prostatectomies, the neoplasm was limited to the prostatic gland. The evolution has been favorable in all patients after 3 years of follow-up, on average. The cases reported herein demonstrate that PHA and foamy adenocarcinoma may be associated and occasionally show overlapping histological criteria. The PHA with foamy changes must be distinguished from conventional foamy adenocarcinoma and PHA because it can closely resemble hyperplastic glands mainly in needle prostatic biopsy.

Pseudohyperplastic prostate carcinoma: histologic patterns and differential diagnosis.

The similarity between some carcinomas and many benign glandular proliferations has been mentioned in the literature for decades. The description of the main histologic features of pseudohyperplastic carcinoma has been very useful in avoiding errors of interpretation, particularly false-negative results. In recent years, we have found some histologic variants of this neoplasm that have not been mentioned previously. In order to classify the different histologic growth patterns and comment on their differential diagnosis, we reviewed the architectural and cytologic features of 34 cases of pseudohyperplastic adenocarcinoma in 2 radical prostatectomies, 4 transurethral resections, and 28 needle biopsies. Growth patterns most commonly observed included nodular, complex, and mixed (nodular and complex) patterns. Other less frequent histologic varieties included adenosis-like pattern, prostatic intraepithelial neoplasia-like pattern, pseudohyperplastic adenocarcinoma with xanthomatous features, and limited pseudohyperplastic adenocarcinoma. Frequent changes in neoplastic glands included papillary infoldings, large/cystic glands, and branching. Criteria associated with malignancy include nuclear enlargement (92%), apparent nucleoli (85%), pink amorphous secretions (78%), and transition to small acinar carcinoma (70%). However, in some biopsies, nuclear atypia was little apparent. Fifteen of the 34 cases were misdiagnosed as benign and 5 as other malignant neoplasms, and included the following diagnoses: hyperplastic nodules (11), prostatic adenosis (2), diffuse adenosis of the peripheral zone (1), benign cystic glands (1), and less frequently other malignant tumors including xanthomatous carcinoma (2), low-grade prostatic adenocarcinoma (2), and atrophic carcinoma (1). It is important to recognize the different growth patterns of this neoplasm in order to avoid an underdiagnosis of malignancy.

Pseudohyperplastic Adenocarcinoma of the Prostate

A 60-year-old man underwent radical prostatectomy after a needle biopsy diagnosis of adenocarcinoma of the prostate with Gleason score 3 þ 3 1⁄4 6 in 4 of 12 cores. Sections of radical prostatectomy tissue showed areas with a somewhat nodular growth of complex glands resembling benign prostatic hyperplasia (fig. 1). This proliferation represents an uncommon variant of usual acinar adenocarcinoma of the prostate known as pseudohyperplastic adenocarcinoma, so called because the light microscopic appearance can simulate that of epithelial hyperplasia in the prostate. This variant, along with other deceptively benign appearing variants (atrophic and foamy gland adenocarcinomas), constitutes a large percentage of needle biopsy cases misdiagnosed as benign. There are no known clinical, radiological or gross features specific for pseudohyperplastic prostatic adenocarcinoma. Microscopically, pseudohyperplastic adenocarcinoma shows papillary infolding (fig. 2), luminal undulations and branching, and cystic dilatation. Pseudohyperplastic prostatic adenocarcinoma in the whole gland may be localized

Pseudohyperplastic prostate adenocarcinoma with signet ring cells mimicking hyperplastic colonic polyp and associated high grade foamy gland carcinoma. A case report

Prostatic adenocarcinoma which closely mimics benign prostatic hyperplasia is adenocarcinoma with pseudohyperplastic pattern. The morphological similarities include large glands with papillary infoldings and branching. However the distinguishing features are crowded glands, nuclear enlargement, occasional to frequent nucleoli and abundant pink intraluminal secretions and crystals. There can be large glands with straight luminal borders. These tumors are not only difficult to diagnose but they are also difficult to grade as Gleason scoring system does not account for this histologic pattern. Some of these tumors have shown extraprostatic extension and it has been recommended that pseudohyperplastic adenocarcinoma should not be regarded as a low grade cancer. This is a case report of prostatic adenocarcinoma with pseudohyperplastic pattern and signet ring cells in the glandular epithelium mimicking colonic hyperplastic polyp. In addition there is an associated pattern of high grade foamy gland carcinoma and occasional signet ring cells in the stroma. This combination has not been described in previous studies.

Fine Needle Aspiration Cytology of Metastatic Prostatic Adenocarcinoma, Pseudohyperplastic Variant

Pseudohyperplastic prostatic adenocarcinoma is a rare histologic variant of prostatic adenocarcinoma that resembles benign nodular hyperplasia. Immunohistochemistry can verify the absence of basal cells, but it is frequently admixed with conventional adenocarcinoma. Because fine needle aspiration cytology is rarely performed in primary prostatic adenocarcinoma, the cytology of the pseudohyperplastic variant has not been described. We experienced a case of metastatic pseudohyperplastic adenocarcinoma in a pulmonary nodule of 75-year-old man. The cytologic smear was mostly composed of large, flat sheets with elongated branching papillae in a clean background. The sheets showed a well-defined honeycomb appearance of tall columnar, regularly arranged monotonous cells with little cytologic atypia. In subsequent prostatic biopsy, pseudohyperplastic variants were identified together with conventional adenocarcinoma of Gleason's grade 3 and 4. The cytologic features of pulmonary nodules were identical to those of pseudohyperplastic components of prostatic adenocarcinoma.

Diagnosis and reporting of limited adenocarcinoma of the prostate on needle biopsy

The diagnosis of limited adenocarcinoma of the prostate is one of the more difficult challenges in surgical pathology. This paper highlights the methodological approach to diagnosing limited cancer, based on a constellation of features more commonly present in adenocarcinoma than benign glands. In assessing small foci of atypical glands on needle biopsy, one looks for differences between the benign glands and the atypical glands in terms of nuclear features, cytoplasmic features, and intraluminal contents. Only a few features, such as glomerulations, mucinous fibroplasia (collagenous micronodules), and perineural invasion are diagnostic in and of themselves for prostate cancer. Immunohistochemistry may be a useful adjunct in the diagnosis of limited adenocarcinoma of the prostate, although as with any immunohistochemical studies, there are problems with both sensitivity and specificity. Basal cell markers, such as high molecular weight cytokeratin and more recently, p63, highlight basal cells found in benign glands, yet are absent in adenocarcinoma of the prostate. However, not all benign glands label uniformly with basal cell markers. Certain mimickers of adenocarcinoma of the prostate are even less frequently labeled uniformly with these stains. Consequently, negative staining in a small focus of atypical glands for basal cell markers is not diagnostic of adenocarcinoma of the prostate. More recently, a marker has been identified that relatively selectively labels adenocarcinoma of the prostate. AMACR will label the cytoplasm of approximately 80% of limited adenocarcinoma of the prostate cases on needle biopsy. In positive cases, not all of the glands will be positive and those that are positive are often not intensely positive. Certain variants of adenocarcinoma of the prostate that are a little more difficult to recognize, such as foamy glands adenocarcinoma, pseudohyperplastic adenocarcinoma, and atrophic adenocarcinoma, are labeled with AMACR in only approximately 60–70% of cases. In addition to problems with sensitivity, AMACR is not entirely specific for adenocarcinoma, and will label almost all cases of high-grade prostatic intraepithelial neoplasia, some foci of adenosis, and even some entirely benign glands. Finally, this paper will briefly cover the significance of atypical or suspicious prostate needle biopsies, and how to report the key diagnostic and prognostic information on needle biopsy.

Diagnosis and reporting of limited adenocarcinoma of the prostate on needle biopsy

The diagnosis of limited adenocarcinoma of the prostate is one of the more difficult challenges in surgical pathology. This paper highlights the methodological approach to diagnosing limited cancer, based on a constellation of features more commonly present in adenocarcinoma than benign glands. In assessing small foci of atypical glands on needle biopsy, one looks for differences between the benign glands and the atypical glands in terms of nuclear features, cytoplasmic features, and intraluminal contents. Only a few features, such as glomerulations, mucinous fibroplasia (collagenous micronodules), and perineural invasion are diagnostic in and of themselves for prostate cancer. Immunohistochemistry may be a useful adjunct in the diagnosis of limited adenocarcinoma of the prostate, although as with any immunohistochemical studies, there are problems with both sensitivity and specificity. Basal cell markers, such as high molecular weight cytokeratin and more recently, p63, highlight basal cells found in benign glands, yet are absent in adenocarcinoma of the prostate. However, not all benign glands label uniformly with basal cell markers. Certain mimickers of adenocarcinoma of the prostate are even less frequently labeled uniformly with these stains. Consequently, negative staining in a small focus of atypical glands for basal cell markers is not diagnostic of adenocarcinoma of the prostate. More recently, a marker has been identified that relatively selectively labels adenocarcinoma of the prostate. AMACR will label the cytoplasm of approximately 80% of limited adenocarcinoma of the prostate cases on needle biopsy. In positive cases, not all of the glands will be positive and those that are positive are often not intensely positive. Certain variants of adenocarcinoma of the prostate that are a little more difficult to recognize, such as foamy glands adenocarcinoma, pseudohyperplastic adenocarcinoma, and atrophic adenocarcinoma, are labeled with AMACR in only approximately 60–70% of cases. In addition to problems with sensitivity, AMACR is not entirely specific for adenocarcinoma, and will label almost all cases of high-grade prostatic intraepithelial neoplasia, some foci of adenosis, and even some entirely benign glands. Finally, this paper will briefly cover the significance of atypical or suspicious prostate needle biopsies, and how to report the key diagnostic and prognostic information on needle biopsy.

Method for Procuring Specific Populations of Viable Human Prostate Cells for Research

A wider range of research can be conducted on viable tissue samples than on fixed or frozen samples. A major obstacle to studying viable prostate tissue samples is the inability to accurately identify cancer on direct examination of unembedded tissue. We used a dissecting microscope to identify cancer in unfixed prostate tissue samples stained on the cut surface with 0.5% aqueous toluidine blue. We measured the diagnostic accuracy of this technique in 25 consecutive prostatectomies, determined the viability of procured samples, and estimated the effect on final pathologic assessment. Both surfaces of a 3- to 5-mm thick cross-section taken midway between base and apex of the prostate were examined. A 4-mm punch biopsy was directed to one benign and one malignant area when clearly present. The dissecting microscope allowed clearcut recognition of carcinoma in 17 of the 25 cross-sections, and carcinoma was confirmed in all 17 (100%). In 8 of 25 cases, no procurement was attempted because no carcinoma was evident in the one cross-section studied. Twenty of 25 cross-sections were adequate for benign tissue procurement; five of the cross-sections were not suitable for procurement because of the presence of extensive carcinoma or atrophy. Seventeen of the 20 were accurately diagnosed as benign (85%); one showed pseudohyperplastic adenocarcinoma, one showed focal high-grade prostatic intraepithelial neoplasia, and one showed urothelial carcinoma in situ. Prostatic epithelium obtained with the technique remains viable and can be separated from stroma. The dissecting microscope technique appears to facilitate rather than interfere with accurate pathologic assessment: extraprostatic extension or positive margins were correctly identified during tissue procurement in three cases. The procedure takes only about 30 minutes.