Differentiated cervical intraepithelial neoplasia-associated invasive cervical squamous cell carcinoma as a source of major cytopathological and surgical pathological discrepancy in Papanicolaou smear screening tests.

INTRODUCTION: Differentiated cervical intraepithelial neoplasia (dCIN) analogous to differentiated squamous intraepithelial neoplasia of the vulva is characterised by the proliferation of atypical cells limited to the basal/parabasal layers. Exfoliative cytology of dCIN has not been investigated. METHODS AND RESULTS: A 46-year-old woman, with a history of normal Papanicolaou (Pap) smear up to 2 years prior to the occurrence of postcoital vaginal bleeding had two consecutive Pap smears, which only revealed atypical squamous cells of unknown significance (ASCUS). The subsequent cervical biopsy revealed dCIN. The cone biopsy showed the invasive cervical squamous cell carcinoma (ICC) that developed from the overlying dCIN. Review of 32 consecutive cases of ICC revealed a second case of dCIN-associated ICC (Group 1) preceded by ASCUS suspicious for high-grade neoplastic cells. In both cases, the ASCUS were keratinised atypical cells without koilocytosis. In addition, there were another seven cases showing focal dCIN associated with extensive usual CIN (Group 2). In comparison with the remaining 24 cases with usual CIN (Group 3), Group 2 lesions occurred in younger patients (mean ages of 36 ± 3 vs 47 ± 9 years) and were associated with shorter intervals after the last normal Pap smears. Pap smears in Group 2 occasionally consisted only of ASCUS cells. CONCLUSIONS: dCIN may occur in the cervix and accounts for a short interval of normal Pap smears and false negative or low-grade Pap smears in ICC.

[Progress in application of machine learning in epidemiology].

Population based health data collection and analysis are important in epidemiological research. In recent years, with the rapid development of big data, Internet and cloud computing, artificial intelligence has gradually attracted attention of epidemiological researchers. More and more researchers are trying to use artificial intelligence algorithms for genome sequencing and medical image data mining, and for disease diagnosis, risk prediction and others. In recent years, machine learning, a branch of artificial intelligence, has been widely used in epidemiological research. This paper summarizes the key fields and progress in the application of machine learning in epidemiology, reviews the development history of machine learning, analyzes the classic cases and current challenges in its application in epidemiological research, and introduces the current application scenarios and future development trends of machine learning and artificial intelligence algorithms for the better exploration of the epidemiological research value of massive medical health data in China.

Progesterone receptor reactivity in renal oncocytoma and chromophobe renal cell carcinoma.

AIMS: To investigate the reactivity for oestrogen and progesterone receptors (ER and PR) in renal oncocytoma (RO) and chromophobe renal cell carcinoma (CHRCC). MATERIALS AND METHODS: Thirty-eight RO, 25 CHRCC, 20 papillary RCC with oncocytic cytoplasm and 10 clear cell RCC with dominant eosinophilic cytoplasm were submitted for immunohistochemistry for ER, PR, CD117 and RCC. RESULTS: All cases of RO and CHRCC displayed moderately positive reactivity for PR. The nuclear reactivity ranged from 60% to 90% in RO and from occasional cells to 70% in CHRCC. In CHRCC, reactivity tended to be more prevalent in areas of tumour cells with eosinophilic cytoplasm. Progesterone reactivity was focal in areas. All RO and most CHRCC were reactive for CD117 and neither RO nor CHRCC was reactive for RCC. CD117 reactivity tended to be more intense in CHRCC than in RO. Negative reactivity for CD117 and positive reactivity for RCC were observed in almost all RCC, as reported in the literature. CONCLUSIONS: PR can be used in combination with CD117 and RCC in the differential diagnosis of RO and eosinophilic variant of CHRCC with other RCC with oncocytic or eosinophilic cytoplasm.

Vascular myxolipoma ("angiomyxolipoma") of the spermatic cord.

We report a case of vascular myxolipoma of the spermatic cord occurring in a 32-year-old man. Clinically, the lesion was mobile and tender. Pathologically, the tumor was encapsulated and rubbery with a beige-yellow gelatinous cut surface. Microscopically, the lesion consisted of adipose tissue with extensive areas of myxoid change and an abundance of thin and thick-walled blood vessels. We consider this tumor a vascular type of myxolipoma and propose the term angiomyxolipoma. The lesion should be distinguished from liposarcoma and aggressive angiomyxoma, which have malignant or aggressive clinical course.

Bilateral primary ovarian squamous cell carcinoma associated with human papilloma virus infection and vulvar and cervical intraepithelial neoplasia. A case report with review of the literature.

Primary squamous cell carcinoma of the ovary is rare. Most cases represent malignant transformation of ovarian teratomas. Other cases are associated with preexisting Brenner tumor or ovarian endometriosis. We report a primary ovarian squamous cell carcinoma in a 40-year-old woman. The patient had recurrent high-grade intraepithelial neoplasia of the vulva (VIN) and recurrent high-grade cervical intraepithelial neoplasia (CIN). Human papilloma virus (HPV) DNA 16/18 was identified in an in situ and invasive carcinoma in the left ovary; CIN and VIN were identified with in situ hybridization with biotinylated DNA probes. Review of the literature revealed nine cases of primary ovarian squamous cell carcinoma not associated with a preexisting ovarian lesion. Three cases were not associated with CIN and occurred in women who ranged in age from 64 to 90 years and did not have carcinoma in situ component. Six cases were associated with CIN, had a carcinoma in situ, and occurred in younger women ranging from 33 to 54 of age. Our case belonged to the latter category. This report raises the possible causal relationship of HPV with primary ovarian squamous carcinoma in the group of middle-aged patients with CIN.

Primary and secondary prostatic adenocarcinoma of the urinary bladder.

Urinary bladder involvement by prostatic adenocarcinoma (PAC) is not well characterized in the literature. Fifteen consecutive cases of PAC diagnosed in the urinary bladder over a period of 10 years were reviewed. All bladder and prostate slides from each patient were evaluated. Eleven patients (group A) had synchronous PAC in the prostate. In these patients, bladder PAC occurred 2 to 11 years after the initial diagnosis of PAC in the prostate and tended to have a higher Gleason score than the original prostatic PAC. Four cases of bladder PAC in group A had areas with features of urothelial carcinoma, with focal positive immunoreactivity for thrombomodulin in 2 cases. Two patients (group B) had undergone radical prostatectomy for PAC 15 years earlier. The lesions in the urinary bladder in both cases showed histopathologic features similar to those seen in the previous prostatic malignancies. Two patients (group C) had histories of previously resected urothelial carcinoma. Bladder PAC was diagnosed at routine follow-up, and repeated prostate biopsy up to 2 years after the diagnosis of bladder PAC showed no evidence of prostatic PAC. PAC in the urinary bladder may be either primary or secondary. Secondary PAC is usually associated with high-grade and high-stage carcinoma in the prostate and may mimic transitional cell carcinoma. Primary bladder lesions may or may not be associated with a history of PAC in the prostate. The prognosis of patients with the primary carcinoma is favorable. HUM PATHOL 32:434-440.

Development of endometriosis from embryonic duct remnants.

Among 18 cases of endometriosis involving ovaries and fallopian tubes, we identified three cases with foci of endometriosis adjacent to the embryonic duct remnants in the fallopian tube. The serial sections of the blocks of tissue containing areas of interest showed segments of embryonic duct remnants with changes suggestive of gradual transformation to endometrial glands. The early changes consisted of replacement of the muscular coat surrounding the epithelium of embryonic duct remnants by the endometrial stroma with positive immunoreactivities for estrogen receptor. Subsequently there were changes of the embryonic duct remnant epithelium into endometrial epithelium with diffuse immunoreactivities for estrogen receptor. The significance of this transformation as a mechanism of development of endometriosis is discussed.

Absence of serum prostate-specific antigen and loss of tissue immunoreactive prostatic markers in advanced prostatic adenocarcinoma after hormonal therapy: a report of two cases.

We report two cases of advanced prostatic adenocarcinoma (PA) showing complete loss of three tissue immunoreactive prostatic markers, ie, prostate-specific antigen (PSA), prostatic acid phosphatase (PAP), and Leu-7 (CD57), with absence of elevated serum PSA level, despite tumor progression after hormonal therapy with or without radiotherapy. The pretreatment serum PAP in the first case and serum PAP and PSA in the second case were elevated. In both cases, the prostatic adenocarcinoma in the initial transurethral resection specimens showed positive immunoreactivity with three prostatic markers. After treatment, in both cases, the serum PSA were undetectable, and tumor cell immunostaining for three prostatic markers was negative. In addition, the posttreatment tumors in both cases showed increased number of tumor cells with neuroendocrine differentiation in comparison those in the pretreatment tumors. Although early PA without elevated serum level of PSA is common, advanced PA with absence of elevated serum PSA, associated with presence of tissue immunoreactive prostatic markers are rare. This is the first report of advanced prostatic adenocarcinomas showing loss of tumor cell prostate-specific markers with absence of elevated serum PSA level after hormonal therapy despite tumor progression.

Pattern of distribution of intraductal and infiltrating ductal carcinoma: a three-dimensional study using serial coronal giant sections of the breast.

The purpose of this study was to establish the 3-dimensional (3D) structure of the breast tissue and to study the distribution and relationship between the intraductal and infiltrating components of ductal carcinoma and other proliferative epithelial lesions of the breast. Thirty mastectomy specimens with infiltrating carcinoma less than 3.0 cm in diameter were serially cut in the coronal plane. Each giant section was divided into small sections for routine processing. Using Photoshop (Adobe) and PowerPoint (Microsoft) software programs, the routinely stained sections were scanned and assembled to reestablish complete giant sections of the breast and subsequently the 3D structure. Intraductal and infiltrating ductal carcinomas, epithelial hyperplasia with atypia, and marked epithelial hyperplasia without atypia were mostly confined to a single duct (27 cases), resulting in an increase in size of the involved breast segment. Three remaining cases included a case of Paget's disease with tumor appearing to spread from one duct system to another system through the epidermis and two cases with multiple separate foci of carcinomas located in different quadrants and accompanied by ductal spread in different lactiferous ducts. Both intraductal and infiltrating carcinomas were often located in the superficial segments (near the subcutaneous tissue) (28 cases). The infiltrating components were often located adjacent to area of pure intraductal carcinoma and were often peripheral (nearer the chest wall than the nipple). Intraductal carcinomas showed a "fanned out" pattern of distribution, frequently extended toward the nipple (with involvement of the nipple or subareolar tissue in 7 cases), and occasionally were seen in the breast tissue peripheral to the infiltrating carcinoma. Multiple ducts with intraductal carcinoma could be seen to be connected with each other with serial sections. However, in at least 6 cases, foci of intraductal carcinomas were separated from each other by segments of duct with benign epithelium. Breast carcinoma often arise from the breast segment close to the subcutaneous tissue. Infiltrating carcinoma lesser than 3.0 cm in diameter is usually located adjacent to the area of pure intraductal. The pattern of spread of intraductal carcinoma has a pyramid-like shape, with the summit toward and occasionally extending up to the nipple. These findings should be considered in the surgical strategy for segmental resections of breast carcinomas.

Active chemotherapy for metastatic stromal cell tumor of the testis.

Metastatic stromal cell tumors of the testis are largely refractory to chemotherapy. We report a case of a young man with widely metastatic testicular stromal cell tumor who achieved complete clinical remission following chemotherapy with etoposide, ifosfamide, cisplatin, and bleomycin.

Light and electron microscopy of the pagetoid spread of germ cell carcinoma in the rete testis: morphologic evidence suggestive of field effect as a mechanism of tumor spread.

The purpose of this study is to investigate the mechanism of tumor spread in the pagetoid spread of germ cell tumors in the rete testis (PSRT). Twenty consecutive cases of germ cell tumor of the testis (9 seminomas, 3 embryonal carcinomas, and 8 teratocarcinomas) were retrieved to identify the cases with PSRT. The areas of pagetoid spread were examined by the serial sectioning of the entire thickness of the tissue block. Available fresh tissue was submitted for electron microscopic study. Ten cases were associated with PSRT and had focal or extensive areas of intratubular germ cell neoplasia (IGCN) in the proximity of the tumor and the rete testis (RT). In the remaining 10 cases, 6 were associated with IGCN distant from the RT and the last 4 were not associated with IGCN. Seminiferous tubules with IGCN were seen connecting with the RT with pagetoid spread. Isolated single intraepithelial tumor cells also were identified at the periphery of the areas with PSRT. Electron microscopic study of the RT of 4 cases with PSRT (2 seminomas, 1 embryonal carcinoma, and 1 teratocarcinoma) revealed desmosome-type junctions between tumor cells with RT epithelial cells. Direct tumor expansion and cell motility as mechanisms of tumor spread in PSRT does not explain the presence of isolated cells and desmosome-type junctions of the tumor cells as demonstrated in this study. The authors believe that the field effect plays an important part in the pathogenesis of this pagetoid spread in the RT. It is likely that this field effect is induced by the germ cell tumor and is operated through the immature germ cells or undifferentiated epithelial cells in the RT adjacent to the tumor cells.

Immunostaining for ret oncogene proteins in papillary thyroid carcinoma: a correlation of ret immunoreactivity and potential of lymph node metastasis.

Ret oncogenes, particularly Ret/PTC, have been associated with the potential of local invasion of papillary thyroid carcinoma (PTC). The purpose of this study was to investigate the correlation between the Ret oncogene expression and the potential of lymph node metastasis of PTC. A total of 107 PTC were microscopically reviewed to identify areas of infiltrating carcinoma (IC). IC was defined as tumor cells disposed in a haphazard pattern and in lobules, nests, follicles, or single cells within a desmoplastic or sclerotic stroma. All cases were submitted to immunostaining for Ret oncogene. There were 36 noninfiltrating PTC with lymph node metastasis in 1 case and 71 infiltrating PTC with lymph node metastasis in 40 cases. For non-PTC, the positive immunoreactivity was often weak to moderate and focal. For infiltrating PTC with IC, the IC displayed strong immunoreactivity. The noninfiltrating component of PTC with IC usually showed stronger reactivity than PTC without an infiltrating component. Furthermore, 36 of 40 metastatic PTC in lymph node were immunoreactive. Three follicular adenomas with areas of scar caused by fine-needle aspiration biopsy were not immunoreactive for Ret. In view of the high potential of infiltrating PTC for lymph node metastasis, distinction of this type of carcinoma from its noninfiltrating form is clinically important. Because immunoreactivity for Ret is usually positive in areas of infiltrating PTC and is often negative or focally positive in noninfiltrating PTC, immunostaining for Ret is helpful to identify infiltrating PTC and distinguish it from changes caused by fine-needle aspiration biopsy in benign thyroid lesions.

Predictive value of extent and grade of ductal carcinoma in situ in radiologically guided core biopsy for the status of margins in lumpectomy specimens.

AIMS: The correlation between the extent and grade of ductal carcinoma in situ (DCIS) in a core needle biopsy of breast, and the presence of an extensive intraductal carcinoma component (EIC) or positive resection margins in a subsequent mastectomy, has not been adequately addressed in the literature. MATERIALS AND METHODS: Seventy-eight core needle biopsies with mammography and mastectomy correlation (27 total mastectomies, 51 lumpectomies) were reviewed. The extent and grade of DCIS in the biopsies were determined and compared with the mammographic findings and the status of the EIC and margins in subsequent mastectomy specimens. RESULTS: Twenty-four cases of core biopsies with at least three foci of low-grade DCIS or at least two foci of high grade DCIS (group I) corresponded in large part to cases of mastectomy with a positive EIC (20/23 cases, or predictive value of 87%). Nine of 15 cases of lumpectomy in this group were associated with margins positive for or close to (less than 0.1 cm from) carcinoma. Thirty-three cases of core biopsies with one or two foci of low-grade DCIS or one focus of high-grade DCIS (group II) were associated with mastectomies with a limited extent of DCIS. Only four of 22 lumpectomy specimens in this group had margins positive for or close to carcinoma. Twenty-one cases of core biopsies without DCIS (group III) represented all five mastectomy specimens without DCIS, and 16 mastectomies with DCIS and negative EIC. None of the 14 cases of lumpectomy in this group had margins positive for carcinoma. The predictive value for EIC status may be even higher if mammographic findings are used in cases with a low number of foci (two foci of low-grade DCIS or one focus of high-grade DCIS in short biopsy cores). CONCLUSIONS: There was a good correlation between the extent and grade of DCIS in core biopsies and the status of EIC in subsequent mastectomy specimens. Core needle biopsies with at least three foci of low-grade DCIS or at least two foci of high-grade DCIS are associated with a greater likelihood of positive or close margins in subsequent lumpectomies. Core biopsies without DCIS are associated with a greater likelihood of negative margins in subsequent lumpectomies.

Adenomatoid tumor of the genital tract: evidence of mesenchymal cell origin.

The objective of this study was to re-examine the histogenesis of adenomatoid tumors. This benign neoplasm is characterized by gland-like structures with a pseudodinfiltrative pattern, usually involving fibromuscular tissue at a certain distance from an overlying surface mesothelium. Twenty cases of adenomatoid tumors and four cases of reactive submesothelial lesions, characterized by marked proliferation of subserosal mesenchymal cells, were reviewed. Nineteen of twenty adenomatoid tumors, including lesions with ill-defined borders, showed no connection with surface mesothelium. At the periphery of small tumors, isolated glands, clusters of epithelioid cells and single epithelioid, and spindled cells showing no connection to adjacent glands or cell clusters were identified. The tumor cells shared features with reactive subserosal stromal cells including an infiltrative pattern and histochemical and immunohistochemical properties. The differences between adenomatoid tumors and reactive submesothelial tissue are quantitative in nature: predominant amount of spindled cells in reactive submesothelial lesions, and predominant amount of gland-like structures in adenomatoid tumors. It is proposed that adenomatoid tumors arise from pluripotent mesenchymal cells that differentiate toward submesothelial cells and eventually mesothelial cells. This differentiation is probably induced by the adjacent submesothelial cells.

Immunohistochemical study of papillary thyroid carcinoma and possible papillary thyroid carcinoma-related benign thyroid nodules.

Recent immunohistochemical studies have identified different antisera that have various degrees of sensitivity and specificity for papillary thyroid carcinoma (PTC). In this study, we performed immunostaining for CK, EMA, HBME, CD57 and CD15 in PTC, and benign thyroid nodular lesions to compare the sensitivity and the specificity of these antisera for PTC. In addition, we studied the patterns of immunostaining of these antisera in benign nodular thyroid lesions displaying a fine chromatin pattern, foci of cells with nuclear grooves, and optically clear nuclei. Fifty-five PTC (composed of 30 papillary variants and 25 follicular variants), 5 follicular carcinomas, 30 follicular adenomas, and 20 thyroid nodular lesions (5 papillary variants and 15 follicular variants) were submitted for immunostaining with CK, EMA, HBME, CD57, and CD15. CK and HBME showed the highest sensitivity and specificity for PTC when an arbitrary cutoff of more than 10% positive cells was considered as positive diagnostic immunostaining for these sera. The other antisera were less sensitive and less specific. One case of PTC showed negative HBME but positive CD15, whereas three papillary variants and two follicular variants of benign thyroid nodules revealed a positive diagnostic HBME immunostaining for PTC and negative CK immunostaining. Any combination of positive diagnostic immunostaining with CK+ HBME, CK+ CD57 or CK+ CD15 has a sensitivity of 95% and specificity of 90% for PTC. Thyroid nodules with a diffuse or focal fine chromatin pattern and focal areas with nuclear grooves or optically clear nuclei displayed immunoreactivity ranging from 0% to 50% of cells. Three of five follicular carcinomas showed negative reactivity for HBME, CD57, and CD15. A combination of immunostaining with CK, HBME and CD57 (or CD15) is a sensitive and specific test for PTC. This panel can be used to rule out thyroid nodules posing a diagnostic problem with PTC. Follicular adenoma and nodules of the thyroid, with a fine chromatin pattern and focal nuclear grooves or optically clear nuclei, displayed an intermediate range of reactivity between reactive thyroid tissue and PTC.

A comparative study of metastatic renal cell carcinoma with correlation to subtype and primary tumor.

Clear cell (CRCC), papillary (PRCC) and chromophobe (CHRC) renal cell carcinoma (RCC) are the three most frequent subtypes of RCC. The rate and distribution of their metastatic lesions have not been well documented. We compared metastatic RCC according to subtype and primary tumor characteristics to better understand their behavior and to aid in the diagnosis of metastatic RCC. Pathology reports and clinical charts related to 283 CRCC, 48 PRCC and 13 CHRCC, including their respective sarcomatoid variants, were reviewed. A hundred and thirty-seven CRCC, 5 PRCC and 1 CHRCC with metastases were identified. CRCC and non-CRCC (PRCC and CHRCC) had different patterns of metastasis and primary tumor growth. CRCC metastases were predominantly distributed in lungs, bone, brain, lymph nodes, and adrenal glands. The associated primary CRCC measured 1.5 to 15 cm, were of all grades and stages, and were often associated with invasion of small or large veins. Three PRCC had regional lymph node metastases, 1 PRCC had both regional and mediastinal lymph node metastases. Bone metastasis was present in 1 case each of PRCC and CHRCC. One PRCC with metastasis solely to regional nodes measured 4 cm. The other 4 cases of PRCC with regional lymph node and/or distant metastases as well as the CHRCC with distant metastases were greater than 8 cm in diameter. In metastasizing and non-metastasizing non-CRCC, invasion of small veins was rare and invasion of renal veins was not seen. We cannot comment with any certainty on the metastatic behavior of CHRCC. In our experience, PRCC tend to loco-regional invasion with lymph node spread. They have a low potential for vascular invasion and distant metastases that likely occur only at late stages of the disease. CRCC has a propensity for vascular invasion and may be associated with distant metastasis at an early stage. Therefore, metastatic RCC at a distant location are most likely to be of CRCC origin than PRCC origin.

Papillary transitional cell carcinoma arising in a calyceal cyst and masquerading as a renal cyst.

We report the case of a 74-year-old man with a papillary transitional cell carcinoma, grade 1-2/3, growing within a bilobated calyceal cyst, measuring up to 8.5 cm in diameter, and masquerading as a simple renal cyst. The cyst was lined by atrophic simple and transitional epithelium and showed intracystic hemorrhage. Leakage of blood into the calyx was probably the cause of the hematuria for which the patient presented. However, with retrograde pyelography and careful gross examination of the excised kidney, no communication of the pyelocalyceal system with the cyst could be identified. By ultrasound examination and computerized tomographic scan the lesion showed several small renal cysts, measuring up to 1.1 cm in diameter, as well as several hepatic parenchymal cysts. To our knowledge, this is the first report of a papillary transitional cell carcinoma arising from a cyst of calyceal origin.

'Minimal deviation' endometrioid carcinoma with oncocytic change of the endometrium.

We report an unusual adenocarcinoma of the endometrium in an 80-year-old woman. The tumor diffusely involved the entire thickness of the myometrium. The cervix, ovaries, and fallopian tubes were unremarkable. Microscopic examination revealed an extremely well-differentiated endometrioid adenocarcinoma with mild cytologic atypia and slightly distorted glands infiltrating almost the entire thickness of the myometrium. In addition, the neoplastic endometrioid cells showed extensive oncocytic change. Endometrial curettings had been interpreted as simple endometrial hyperplasia with eosinophilic metaplasia. The significance of this lesion is discussed in terms of possible confusion with benign endometrial lesions as well as benign cervical lesions.

Incidental prostatic adenocarcinomas and putative premalignant lesions in TURP specimens collected before and after the introduction of prostrate-specific antigen screening.

BACKGROUND: Since the introduction of prostate-specific antigen (PSA) screening for the detection of prostatic adenocarcinoma (PCA), there has been an increase in the incidence of stage T1c PCA. The purpose of this study was to compare the frequency of incidental PCA found in transurethral resection of prostate (TURP) specimens for a 14-month period during 1989-1990 (before PSA screening was available) with the incidence of PCA for a 32-month period during 1997-1999 (after PSA screening became available). DESIGN: Consecutive TURP specimens from the 2 time periods were reviewed to identify incidental PCA, prostatic intraepithelial neoplasia (PIN), and atypical adenomatous hyperplasia (AAH). Cases of TURP for palliative treatment of known advanced PCA were excluded from the study. All TURP specimens were fixed in 10% buffered formalin and were processed according to the same protocol. RESULTS: We reviewed 533 and 449 TURP specimens for the time periods 1989-1990 and 1997-1999, respectively. Comparison of the results for these 2 time periods revealed that the combined prevalence of T1a and T1b PCA decreased over time from 12.9% to 8.0% (P =.06) with the introduction of PSA screening. A new group of T1c PCA was established in the post-PSA screening period of 1997-1999. There were no statistically significant differences in the incidences of T1a PCA, PIN, and AAH in TURP specimens for the 2 time periods. CONCLUSION: The decreased incidence of T1b PCA in TURP specimens for the 1997-1999 period represents a shift in PCA staging. Some PCAs previously staged as T1b are now staged as T2 carcinomas, as a result of PSA screening and earlier clinical detection. The introduction of PSA screening has had no influence on the incidence of T1a PCA, PIN, or AAH in TURP specimens.