Histopathological and morphometric analysis of atypical adenomatous hyperplasia of human cirrhotic livers

Atypical adenomatous hyperplasia (AAH) is a hyperplastic parenchymal nodular change in the cirrhotic liver, in which overt hepatocellular carcinoma (HCC) occasionally arises. AAH is defined as a sizable hepatocellular nodule with a variable degree of hepatocellular atypia not regarded as HCC, and is different from ordinary adenomatous hyperplasia in which hepatocellular atypia is absent. In the present study, we attempted to evaluate carcinogenetic processes and to find histological variables which indicate malignant transformation in AAH, using 49 surgically resected or autopsied nodules. AAH frequently showed morphological heterogeneity. Atypical lesions within AAHs were divisible into the following three categories from overall histopathological appearances: malignant (A), equivocal (B), or non-malignant (C) lesions. Analysis of combination of these three lesions, which were frequently intermixed in a given AAH, suggested that B lesions appear subsequent to C lesions, and A lesions finally appear in AAH nodules. Among the 14 histological variables, enlargement, hyperchromasia and irregular contour of nuclei were found to correlate well with A lesions. Increased nuclear density, iron resistance, reduction of reticulin fibres, clear cell change, sinusoidal dilatation and presence of abnormal arteries were suggestive of A or B lesions. Nuclear deviation toward the sinusoids, acinar and compact arrangements, fatty change and Mallory's hyaline alone were not useful indicators of A or B lesions. These results indicate that AAH is a preneoplastic or borderline lesion in which overt HCC is likely to evolve through several steps. Although a needle liver biopsy is a useful tool for diagnosis of benign, equivocal and malignant hepatocellular nodular lesions, the needle biopsy specimen should be carefully evaluated by considering the morphological heterogeneity of the AAH and a variable combination of 14 histological variables.     

Argyrophilic nucleolar organizer regions and alpha-fetoprotein in adenomatous hyperplasia in human cirrhotic livers.

Recently, adenomatous hyperplasia (AH) of the liver has been suspected as a precancerous lesion in human hepatocarcinogenesis. The authors examined 75 cases of AH from 42 cirrhotic livers, using staining of argyrophilic nucleolar organizer regions (AgNORs). These reflect proliferative cell activity. Findings in AH were compared with those seen in hepatocellular carcinoma (HCC) and other chronic liver diseases. Expression of alpha-fetoprotein (AFP) was also examined immunohistochemically. The authors classified AH into three types: ordinary (OAH), atypical (AAH), and AH with focal malignancy (FM). OAH implies a lack of atypia; AAH represents AH with structural and cellular atypia but without the features of overt carcinoma; and FM denotes AH with foci of overt HCC. Forty of the 75 cases of AH were categorized as OAH, 19 as AAH, and 16 as FM. The noncancerous areas of FM had features of AAH. The mean number of AgNORs in AH was intermediate between that seen in cirrhosis (2.93) and HCC (6.18) and showed a step-wise increase in the following order: OAH (2.95), AAH (3.89), noncancerous areas in FM (4.58), and malignant foci in FM (5.71). There was no significant difference in AgNOR counts between OAH and cirrhosis. AgNOR counts in AAH and FM were significantly higher than those of OAH, and lower than those of HCC. AFP was positive in 12 of 25 HCCs and in malignant foci of 3 FM lesions, but it was absent in OAH and AAH. These data suggest that OAH has a limited capacity for proliferation but that AAH and FM are much more replicative. The latter two conditions are probably preneoplastic lesions or early forms of HCC.     

A Histopathological Analysis of Five Cases of Adenomatous Hyperplasia Containing Minute Hepatocellular Carcinoma

We present five cases of adenomatous hyperplasia (AH) containing minute hepatocellular carcinoma (HCC) in cirrhotic liver. All the patients were Japanese, four males and one female, ranging in age from 60 to 80 years. Two of the specimens were obtained at surgery and the others at autopsy. The AH specimens ranged from 2.0 to 3.0 cm in diameter, and the maximum diameter of HCC foci in the AH was 2.0 cm. Histologically, apart from the HCC foci, the AH specimens showed intrinsic atypia, suggesting preneoplastic change. These features included an increase of both cellularity and the nucleo cytoplasmic ratio, distortion of cord structure and pseudoacinar formation. Ail of the AH specimens contained typical portal triads. Details of diagnostic imaging were also obtained in four cases. The findings of the present study support the possibility that AH with intrinsic atypia is a preneoplastic lesion of HCC. The sequence of "adenomatous hyperplasia with intrinsic atypia HCC foci" would thus represent part of the early phase of hepatocarcinogenesis in humans.     

A histopathological analysis of five cases of adenomatous hyperplasia containing minute hepatocellular carcinoma.

We present five cases of adenomatous hyperplasia (AH) containing minute hepatocellular carcinoma (HCC) in cirrhotic liver. All the patients were Japanese, four males and one female, ranging in age from 60 to 80 years. Two of the specimens were obtained at surgery and the others at autopsy. The AH specimens ranged from 2.0 to 3.0 cm in diameter, and the maximum diameter of HCC foci in the AH was 2.0 cm. Histologically, apart from the HCC foci, the AH specimens showed intrinsic atypia, suggesting preneoplastic change. These features included an increase of both cellularity and the nucleo-cytoplasmic ratio, distortion of cord structure and pseudoacinar formation. All of the AH specimens contained typical portal triads. Details of diagnostic imaging were also obtained in four cases. The findings of the present study support the possibility that AH with intrinsic atypia is a preneoplastic lesion of HCC. The sequence of "adenomatous hyperplasia with intrinsic atypia-HCC foci" would thus represent part of the early phase of hepatocarcinogenesis in humans.     

Premalignant lesions of the prostate

Two putative premalignant lesions of the prostate have been identified. Prostatic intraepithelial neoplasia (PIN) is characterized by proliferation and anaplasia of cells lining ducts and acini. Atypical adenomatous hyperplasia (AAH) consists of a localized proliferation of small round glands without cytologic atypia. PIN and AAH may be confused with well-differentiated carcinoma as well as florid hyperplasia, basal cell hyperplasia, transitional metaplasia, seminal vesicular epithelium, and atypia due to inflammation, infarction, and radiation. These premalignant lesions appear to have a high predictive value for carcinoma, and their presence on prostatic biopsy warrants further search for concurrent invasive adenocarcinoma. The use of strict morphologic criteria and uniform nomenclature will ensure standardization in the diagnosis of premalignant lesions of the prostate.     

Hepatocarcinogenesis in liver cirrhosis: imaging diagnosis.

Hepatocellular carcinoma (HCC) frequently occurs in association with liver cirrhosis, as chronic liver disease is one of the most important factors in carcinogenesis. In addition to HCCs, recent reports of pathologic studies of resected specimens from cirrhotic liver describe associated small nodular lesions such as regenerative nodule, dysplastic nodule (adenomatous hyperplasia), and dysplastic nodule with subfocus of HCC (early HCC). In hepatocarcinogenesis of the cirrhotic liver, a regenerative nodule might be the first step in the development of HCC, going through phases of dysplastic nodule, early HCC and early advanced HCC in a multistep fashion. Fortunately, recent advances in various imaging techniques have facilitated the verification of these nodules. In this review, new nomenclature of small hepatocellular nodules, and detection and characterization of hepatic nodules in carcinogenesis with various imaging techniques are described with focus on the premalignant lesions and early stage of HCC. In addition, the efficacy of various imaging techniques for diagnosing them is discussed. Although the terms and definitions of these nodules are still variable and controversial, familiarity with the concept of these borderline lesions is important.     

Atypical adenomatous hyperplasia (adenosis) of the prostate: DNA ploidy analysis and immunophenotype

Atypical adenomatous hyperplasia (AAH) of the prostate is a microscopic proliferation of small acini that may be mistaken for adenocarcinoma. Although some data suggest that AAH is associated with adenocarcinoma arising in the transition zone, the clinical significance of this lesion is uncertain. Therefore we studied the DNA ploidy pattern and immunophenotype of AAH as compared with nodular hyperplasia and well-differentiated adenocarcinoma in 23 formalin-fixed, paraffin-embedded, whole-mounted retropubic prostatectomies. Representative sections were immunostained for keratin 34beta-E12, chromogranin, bcl-2, c-erbB-2, ki67-MIB1, and factor VIII (microvessel density). DNA ploidy was determined by image analysis and Feulgen-stained sections. There were rare scattered immunoreactive cells for chromogranin, bcl-2, and c-erbB-2 in nodular hyperplasia and AAH (mainly in the basal cell compartment) and in carcinoma. The ki67-MIB1 labeling index was different between nodular hyperplasia and AAH (p<0.001) and carcinoma (p=0.003) but not between AAH and carcinoma (p=0.203). Microvessel density was different between AAH and carcinoma (p=0.001) but not between nodular hyperplasia and AAH (p=0.105) or carcinoma (p=0.0820). All foci of nodular hyperplasia, AAH, and carcinoma were diploid. Ploidy status and our selected panel of antibodies did not discriminate among these 3 entities reliably.     

‘Atypical adenomatous hyperplasia’ in liver cirrhosis: low-grade hepatocellular carcinoma or borderline lesion?

Adenomatous hyperplasia, defined as a sizable parenchymal nodule in cirrhosis, was examined morphologically. Ninety-seven nodules of adenomatous hyperplasia were obtained from 47 cirrhotic livers and were divided into 'ordinary' (44 nodules) and 'atypical' (53 nodules) types. The former consisted of hepatocytes similar to those of the surrounding liver, and showed regularly distributed portal tracts. The latter type was composed of hepatocytes showing nuclear atypia, relative to the surrounding liver, and showed irregular or sparse portal tracts. Atypical nodules were histologically heterogeneous, possessing areas of normo-trabecular, compact, pseudoglandular and/or scirrhous patterns. Several cytological changes, such as clear cell change, small or large cell change and fatty change, were intermingled variably within a given nodule. Atypical nodules showed expansive and/or replacing growth into the surrounding liver. Atypical hepatocytes also infiltrated into the fibrous septa and portal tracts. Foci of overt hepatocellular carcinoma were found in 11 of the 53 atypical nodules. These findings suggest that ordinary adenomatous hyperplasia may be a large-sized regenerative nodule, while atypical adenomatous hyperplasia may be a hepatocellular neoplasm, a peculiar form of low-grade hepatocellular carcinoma or borderline lesion, in which overt hepatocellular carcinoma is likely to evolve through multiple steps.     

An autopsy case of metastatic foci of hepatocellular carcinoma in adenomatous hyperplasias of the liver.

Adenomatous hyperplasia of the liver is known as a preneoplastic or early developmental stage of hepatocellular carcinoma, in which overt malignant foci occasionally develop. We have recently experienced an autopsy case (a 70-year-old male) of liver cirrhosis with hepatocellular carcinoma and two nodules of adenomatous hyperplasia. The latter two nodules contained several microscopic foci of moderately differentiated hepatocellular carcinoma. There were a number of tumor microemboli in portal vein branches within areas of adenomatous hyperplasia in addition to areas surrounding cirrhotic liver, some of which grew into the parenchyma of adenomatous hyperplasia and cirrhotic regenerative nodules. These findings and the fact that adenomatous hyperplasia contained portal tracts including portal venous branches, suggest that malignant foci in adenomatous hyperplasia contained portal tracts including represent metastases from hepatocellular carcinoma in other parts of the liver via the intrahepatic portal venous system.     

An Autopsy Case of Metastatic Foci of Hepatocellular Carcinoma in Adenomatous Hyperplasias of the Liver

Adenomatous hyperplasia of the liver is known as a preneoplastic or early developmental stage of hepatocellular carcinoma, in which overt malignant foci occasionally develop. We have recently experienced an autopsy case (a 70-year-old male) of liver cirrhosis with hepatocellular carcinoma and two nodules of adenomatous hyperplasia. The latter two nodules contained several microscopic foci of moderately differentiated hepatocellular carcinoma. There were a number of tumor microemboli in portal vein branches within areas of adenomatous hyperplasia in addition to areas surrounding cirrhotic liver, some of which grew into the parenchyma of adenomatous hyperplasia and cirrhotic regenerative nodules. These findings and the fact that adenomatous hyperplasia contained portal tracts including portal venous branches, suggest that malignant foci in adenomatous hyperplasia of the liver in this case might represent metastases from hepatocellular carcinoma in other parts of the liver via the intrahepatic portal venous system. Acta Pathol Jpn 41: 911 915, 1991.     

Adenomatous hyperplasia of the liver resembling focal nodular hyperplasia in patients with chronic liver disease

Two nodules of hepatic adenomatous hyperplasia (AH) resembling focal nodular hyperplasia were found in two patients with cirrhosis or chronic active hepatitis. Imaging techniques suggested that the nodules were hepatocellular carcinoma. Pathological examination showed that the nodules (approximately 1.0 cm in diameter) were clearly demarcated from the surrounding liver tissue, and contained foci of scar-like fibrosis in the centre of the nodules. Microscopically, they contained portal tracts and fulfilled the criteria of AH. A large number of arteries were present in the central scarlike fibrosis as well as in the parenchyma of the nodules. There were foci of mildly atypical hepatocytes in one nodule but no cellular atypia in the other. Morphometric analysis showed that the cumulative luminal area of arteries per unit area was much greater in the nodules than in the extranodular liver tissues, while the cumulative luminal area of portal veins per unit area was much less in the nodules than in the extranodular liver tissues. Although the pathogenesis is unclear, these nodules might have developed through localized vascular changes associated with chronic liver disease, may have arisen from pre-existing arterial malformation, or may represent the early stages of angiogenesis in hepatocarcinogenesis.     

Detection of chromosomal aberrations in well-differentiated hepatocellular carcinoma by bright-field in situ hybridization.

Differentiation between well-differentiated hepatocellular carcinoma (HCC) and nonmalignant lesions with increased cellular proliferation may be difficult in needle biopsies. Based on recurrent chromosome aberrations known for HCC, we developed a nonfluorescent in situ hybridization technique that allows combination with morphological analysis in bright-field microscopy. Fourteen biopsies of HCC and 31 samples of regenerative nodules (n = 10), chronic hepatitis (n = 10), fibrosis or cirrhosis of unknown origin (n = 5), focal nodular hyperplasia (n = 2), primary biliary cirrhosis (n = 2), steatosis (n = 1), and adenomatous hyperplasia (n = 1) were analyzed with probes specific for the centromeric regions of chromosomes 1, 6, 7, and 8. After microwave pretreatment and in situ hybridization, signals were detected using a tyramine-based system and AEC as substrate. Evaluation of signals was done by conventional bright-field microscopy. Using this approach, aberrant counts were seen for at least one chromosome in 12/14 cases of HCC. In contrast, none of the nonmalignant lesions revealed aberrant counts for any of the chromosomes analyzed. In conclusion, this new combination of in situ hybridization and tyramine amplification allows fast and reliable evaluation of chromosome aberrations in a histomorphological context similar to paraffin immunohistochemistry. Registration of imbalances contributes to a reliable differentiation between malignant and nonmalignant lesions of the liver.     

Immunohistochemistry and angiography in adenomatous hyperplasia and small hepatocellular carcinomas

The sinusoidal structure and blood supply of 38 liver nodules less than 2 cm In diameter were Investigated. There were 18 cases of adenomatous hyperplasia (AH) and 20 cases of hepatocetlular carcinoma (HCC). Growth pattern, encapsulation and vascularity were examined, and Immunohistochemistry performed for factor VIII related antigen (factor VIII), type IV collagen (collagen IV), lamlnln and CD68. There were significant differences between AH and small HCC, except for the expression of CD68. There were differences In tumor size, vasculartty and the components of the basement membrane between AH and small, well differentiated HCC. The cases of AH were supplied by the portal system and maintained the sinusoidal structure, but small well-differentiated HCC were supplied by a mixture of portal and arterial vessels. In spite of their small size, moderately and poorly differentiated HCC had capillary and were supplied by branches of the hepatic artery.     

Histological study of PIVKA-II expression in hepatocellular carcinoma and adenomatous hyperplasia

Although serum concentration of protein induced vitamin K absence or antagonist II (PIVKA-II) has been widely used for diagnosing hepatocellular carcinoma (HCC), little information is available concerning tissue PIVKA-II as an immunohistochemical marker for liver histology. In this study, we examined the expression of PIVKA-II in precancerous nodules (adenomatous hyperplasia) and various differentiation grades of HCC by immunohistochemical study using the monoclonal anti-PIVKA-II antibody (MU-3). We examined the relationship between tissue PIVKA-II staining and serum PIVKA-II level, tumor histology and tumor size. PIVKA-II was mainly detected in the cytoplasm of the HCC cells. The positive rates of PIVKA-II were as follows: adenomatous hyperplasia (AH), 0% (0/9); well-differentiated HCC, 65% (15/23); moderately differentiated HCC, 85% (22/26); poorly differentiated HCC, 54% (7/13). The expression of tissue PIVKA-II staining in moderately differentiated HCC was significantly higher than in well- or poorly differentiated HCC, whereas the serum PIVKA-II level in poorly differentiated HCC was higher than well- or moderately differentiated HCC. There was no relationship between the expression of PIVKA-II in cancer tissues and serum levels of PIVKA-II. Immunohistochemical studies revealed that PIVKA-II was expressed even in small-sized or well-differentiated HCC cells, but expression was not detected in AH. It was concluded that PIVKA-II is a useful immunohistochemical marker, even in small-sized or well-differentiated HCC.     

Distinguishing well-differentiated hepatocellular carcinoma from benign liver by the physical features of fine-needle aspirates.

Distinguishing well-differentiated hepatocellular carcinoma (HCC) from benign hepatic lesions is challenging for pathologists in limited diagnostic material such as needle-core tissue biopsy and fine-needle aspiration (FNA) biopsy. The objective of this study is to test a hypothesis that the fortification of liver by reticulin along single cell plates should protect benign hepatic lesions from breakdown by the force of aspiration and smearing, whereas the decreased reticulin in well-differentiated HCC would result in finely granular FNA smear. The study involved FNA biopsies of 67 cases of well-differentiated HCC and 109 cases of benign hepatic lesions, including cirrhosis (22), liver cell adenoma (8), steatosis (7), focal nodular hyperplasia (6), liver with cholestasis (6), and unremarkable liver sampled from nodular hepatic lesions consistent with the regenerative nodules (60). A slide with the most sample from each case by gross inspection was mixed together. Two observers blinded to the diagnoses were asked to separate the slides into two groups based on smear characteristics by gross inspection. Fragments of rigid fine-needle cores was present in 109 out of 109 cases of benign hepatic lesions but absent in 61 out of 67 cases of well-differentiated HCC, which presented as finely granular smears. The difference is statistically significant. (P<0.001, df=1, chi2=149.3). Using the physical characteristic of liver aspirates as the screening test for malignancy, the sensitivity is 91%, specificity is 100%, positive predictive value is 100%, negative predictive value is 94.8%, and efficiency is 96.6%. In conclusion, the smear characteristics of liver samples in FNA biopsy correlate to their reticulin status on histology. This physical characteristic can be used as the first clue to distinguish malignant and benign liver aspirates prior to microscopic examination.     

Mallory body clustering in adenomatous hyperplasia in human cirrhotic livers: report of four cases

We report four cases of liver cirrhosis in which seven nodules of adenomatous hyperplasia (AH) were present. Each nodule contained one to several foci of hepatocytes with Mallory bodies (MBs). All of these foci were well-circumscribed lesions located within the nodules of AH. The cells containing MBs showed variable degrees of atypia. At least two of the foci were considered to represent a recent proliferation of the cells containing MBs, possibly premalignant foci, because they showed resistance to the accumulation of stainable iron in siderotic background. From these observations, it was suggested that the MB-containing hepatocellular clusters in AH might have occurred as the result of proliferation in small foci and that at least some of them may be related to hepatocarcinogenesis in humans.     

Immunohistochemical detection of XIAP and p63 in adenomatous hyperplasia, atypical adenomatous hyperplasia, bronchioloalveolar carcinoma and well-differentiated adenocarcinoma.

The critical distinction of bronchioloalveolar carcinoma (BAC), well-differentiated adenocarcinoma (WDAC) of lung, adenomatous hyperplasia (AH) and atypical adenomatous hyperplasia (AAH), is based on morphological criteria alone, and is therefore potentially subjective. We examined expression of two markers, X-linked inhibitor of apoptosis protein (XIAP), the most potent of the inhibitor of apoptosis protein (IAP) family, and p63, a marker of bronchial reserve cells (BRC) and squamous cells, in these entities. H&E slides of 37 tissue blocks from 27 patients were reviewed and classified as AH (n=7), AAH (n=8), BAC (n=9) and WDAC (n=13). Immunostaining was performed on 4 mum sections with monoclonal anti-XIAP and monoclonal anti-p63. Granular or heterogeneous cytoplasmic staining for XIAP and nuclear staining for p63 were considered positive. Neither XIAP nor p63 were detected in normal lung alveolar cells. All seven AHs were negative for XIAP and negative or focally positive for p63. All eight AAHs were positive for XIAP and displayed p63 positivity in scattered cells. All BACs displayed XIAP positivity, which ranged from focal/weak to diffuse/strong. p63 was negative in seven and focally positive in two of nine BACs. Twelve of 13 WDACs showed XIAP positivity in a similar pattern to BAC; all were negative for p63. One aberrant case diagnosed on H & E as WDAC was negative for XIAP but strongly positive for p63. Significant XIAP expression appears to be useful for distinguishing AAH from AH. Commonality of XIAP staining in AAH, BAC and WDAC supports the possibility that AAH may be a pre-malignant lesion. The rarity of p63 expression confirms previous reports and supports a nonbronchial histogenesis of these entities. In contrast, diffuse p63 staining may facilitate the identification of rare cases that may have been misclassified as alveolar in origin based on morphology but may be of BRC origin.     

Non-neoplastic nodular lesions in the liver

The classical nomenclature and categorization of neoplastic and non-neoplastic nodular lesions of the liver are being revised due to the tremendous volume of information recently published on this issue. The diagnostic histopathology of non-neoplastic nodular (tumor-like) lesions of the liver that are recognizable in biopsied, surgically resected and autop sied livers is reviewed using current terminology. Generally, such nodules are infrequent and even rare in routine liver specimens. Non-neoplastic nodules include focal nodular hyperplasia, nodular regenerative hyperplasia, compensatory hyperplasia of the liver, pseudonodule of the liver demonstrable by angiography, partial nodular transformation, focal fatty change, nodular hepatic area shown by modified angiography, cirrhotic large regenerative nodule with variable atypia, anoxic pseudolobular necrosis, intrahepatic bile duct adenoma, biliary and mesenchymal hamartoma, and mesenchymal nodular lesions such as inflammatory pseu-dotumor and pseudolymphoma, pseudolipoma, peliosis hepatis, solitary necrotic nodule, and so on. Some of these develop preferentially in non-cirrhotic or cirrhotic livers, while others occur with similar prevalence in cirrhotic and non-cirrhotic livers. Some occur multiply or diffusely and others singly. As to the pathogenesis of these nodules, it is speculated that hyperplasia due to disturbed intrahepatic circulation or hormonal imbalance, preneoplastic characteristics, abnormal metabolic disturbance, hamartoma or focal necrobiotic processes, and infection have a role. Knowledge and awareness of these non-neoplastic nodular lesions are necessary for precise diagnosis and differentiation of these nodular lesions from neoplastic hepatic nodules.     

Nodular histiocytic/mesothelial hyperplasia: a potential pitfall

We present five cases of nodular histiocytic/mesothelial hyperplasia (two peritoneal, two pulmonary, and one pericardial) with identical microscopic features. All the lesions were biphasic and composed of cohesive monotonous epithelioid clusters of polygonal or oval cells with round or deeply grooved nuclei in association with darker cuboidal cells. Because of the increased cellularity and monotonous histologic pattern with some degree of cytologic atypia, neoplastic processes were seriously considered in the differential diagnoses. The majority of the cells marked as histiocytes by immunostain. A few scattered individual cells or small epithelial cell clusters were confirmed by calretinin stain to be mesothelial cells. The histologic patterns of the current lesions, irrespective of the location, were identical to nodular histiocytic/mesothelial hyperplasia. Histiocytic proliferations can be erroneously confused with primary mesothelial lesions or neoplasms such as granulosa cell tumor, eosinophilic granuloma, chronic myelogenous leukemia, and carcinoma. The purpose of this article is to describe the clinicopathologic features of nodular histiocytic/mesothelial hyperplasia and help familiarize pathologists with this lesion to prevent an erroneous diagnosis, particularly when it occurs in locations where mesothelial cells are not normally present.     

Verumontanum mucosal gland hyperplasia is associated with atypical adenomatous hyperplasia of the prostate

BACKGROUND: Verumontanum mucosal gland hyperplasia (VMGH) and atypical adenomatous hyperplasia (AAH) are both small glandular proliferations that are histologically and topographically unique. METHODS: One hundred ten randomly selected, whole-mount, radical prostatectomy specimens were reviewed to assess independently the normal histology of the prostatic urethra and periurethral area and the association of AAH with other pathologic features, including VMGH. The degree of nodular hyperplasia was evaluated by total prostate weight for comparison purposes. RESULTS: Atypical adenomatous hyperplasia was found in 37 cases (33.6%) and was nearly always (32/37) associated with nodules of nodular hyperplasia. Verumontanum mucosal gland hyperplasia was present in 32 cases (29.1%; 21 with AAH, 11 without AAH). There was a significant association between presence of VMGH and AAH (P <.001, Fisher exact test). The degree of nodular hyperplasia was not significantly different between prostates with and without VMGH or AAH. CONCLUSIONS: These results suggest that AAH and VMGH occur more commonly in prostates when the other is also present.