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The significance of thymidine phosphorylase activity in hepatocellular carcinoma and chronic diseased livers: a special reference to liver fibrosis and multicentric tumor occurrence.

The role of thymidine phosphorylase (TP), an angiogenic factor, in hepatocellular carcinoma (HCC) remains unclear. The aim of this study was to clarify the significance of TP in HCC. Thirty-seven patients with HCC, who underwent hepatectomy, were included. The TP activity in both cancerous and non-cancerous parts of livers were measured by an enzyme-linked immunosorbent assay. Another 11 patients without HCC were used to evaluate the TP activity in the non-cancerous parts of livers. Both the cancerous and non-cancerous TP activities were clinico-pathologically investigated with special reference to the multicentric occurrence of HCCs and the degree of liver fibrosis; consisting of normal, fibrosis and cirrhosis. The TP activity in the cancerous part was 94.6 +/- 70.2 U/mg protein, while that in non-cancerous parts of the liver was 80.9 +/- 48.8 U/mg protein. No significant difference was observed. The TP activity in the cancerous part did not correlate with any clinicopathological variables, such as tumor differentiation, portal vein invasion, intrahepatic metastases and prognosis. However, the TP activity in the non-cancerous parts of the liver correlated with the degree of fibrosis (normal/fibrosis/cirrhosis = 34:74:90 U/ mg protein, respectively). Furthermore, regarding the correlation between TP activity in the non-cancerous parts and the simultaneously multicentric occurrence of HCC, the TP activity in the multicentric group (n = 8; 121 U/mg protein) was significantly higher than that in the non-multicentric group (n = 29; 70 U/mg protein). The TP activity in the non-cancerous parts increased in proportion to the degree of liver fibrosis. Furthermore, it is suggested that the higher TP activity in the non-cancerous part is related to the multicentric occurrence of HCCs.

Adult↗

Sacral radiculopathy secondary to multicentric osteosarcoma.

STUDY DESIGN: A case of multicentric osteosarcoma presenting with sacral radiculopathy is reported. OBJECTIVE: To present unusual clinical and radiologic findings of multicentric osteosarcoma. SUMMARY OF BACKGROUND DATA: Multicentric osteosarcoma is a rare variant of osteosarcoma. To the authors' knowledge, no cases of multicentric osteosarcoma presenting as sacral radiculopathy have been reported previously. METHODS: A 14-year-old boy had a large sacral tumor extending into the spinal canal, which was found to account for the initial symptoms, which mimicked those of herniated nucleus pulposus. At diagnosis, a bone survey showed multiple foci of osteosarcoma in the long bones. RESULTS: The patient was treated with chemotherapy, but died of the disease 8 months after the initial presentation. CONCLUSION: Multicentric osteosarcoma should be considered in the differential diagnosis for a pediatric patient with low back pain and sciatica.

Adolescent↗

Multicentric adenocarcinoma of the lung: CT-pathologic correlation.

To evaluate the sensitivity of computed tomography (CT) in detecting multicentric primary bronchogenic adenocarcinoma manifesting as a pulmonary nodule, the authors reviewed CT scans and pathologic specimens of 158 consecutive patients who underwent resection of a pulmonary nodule. Two independent observers assessed the scans without knowledge of the pathologic findings. Lung specimens were fixed in inflation and sectioned transversely, analogous to the plane of the CT scans. In 88 patients the nodule represented adenocarcinoma. Multicentric adenocarcinoma was present in 19 of these patients (22%). The sensitivity of CT in correctly detecting the presence and location of two or more lesions was 0.63 and 0.68 for two observers, with a specificity of 0.86 for both. The CT appearance of multicentric disease varied from well-defined nodules to ill-defined hazy opacities simulating pneumonitis. The data indicate that (a) multicentric adenocarcinomas are more common than generally reported in the literature and (b) meticulous evaluation of CT images enables detection of multicentricity in a high percentage of cases.

Adenocarcinoma↗

Multicentric angiofollicular lymph node hyperplasia with peripheral neuropathy, pseudotumor cerebri, IgA dysproteinemia, and thrombocytosis in women. A distinct syndrome.

Four women with multicentric angiofollicular lymph node hyperplasia had a distinct clinical syndrome characterized by peripheral neuropathy, pseudotumor cerebri, IgA dysproteinemia, and thrombocytosis. The nodes displayed typical morphologic changes of the plasma cell variant of multicentric angiofollicular lymph node hyperplasia. The pathologic changes are morphologically distinct from angioimmunoblastic lymphadenopathy with dysproteinemia although clinical similarities do exist. In these four cases, the lymphadenopathy was usually bulky and multicentric. There was frequent splenic involvement. The neuropathies were severe and disabling. Clinical courses have been variable with some responses to therapy with steroids and alkylating agents. No neoplastic transformations have occurred. Multicentric angiofollicular lymph node hyperplasia may represent a reactive lesion in which the antigenic stimulus is unknown but results in follicular hyperplasia, angiogenesis, and the systemic manifestations of hyperimmune stimulation. We believe this clinical syndrome may represent a distinct variant of multicentric angiofollicular lymph node hyperplasia, and it requires close observation for neoplastic transformation and other complications of its multisystem nature.

Biopsy↗

Parameters predictive of multicentricity in renal cell carcinoma.

Over a 3-year period, 83 radical nephrectomies were performed for renal cell carcinoma. The preoperative radiologic investigations and pathology were reviewed. The incidence of multicentricity of the tumors was correlated with various clinical and pathologic parameters. These included polar location, histologic type, histologic grade (divided into low: Fuhrman grade 1 to 2; and high: Fuhrman grade 3 to 4), size on pathology, pathologic stage, capsular invasion, microscopic vascular invasion, renal vein or inferior vena cava (IVC) involvement, collecting system involvement, lymph node metastases and adrenal gland metastases. The incidence of multicentricity was 9/83 (11%). On univariate analysis, no factors were predictive of multicentricity. On logistic regression analysis, microscopic vascular invasion (p=0.021) and tubulo-papillary histology (p=0.049) were the only significant independent predictors of multicentricity. A model incorporating these parameters missed all multicentric tumors.

Journal Article↗

The intraoperative incidence of detectable bilateral and multicentric disease in papillary cancer of the thyroid.

This is a prospective study to determine the incidence of grossly detectable multicentric and bilateral cancer at operation in patients who, before surgery, were believed to have a unilateral lesion. The opposite lobe was inspected at the time of operation and the surgeon made a determination as to whether there was bilateral and/or multicentric disease present. A total thyroidectomy was then carried out and the accuracy of the surgeon's judgment was established by permanent-section pathologic examination. Fifteen of the 44 patients were assessed to have gross bilateral disease. Thirteen of these were confirmed by pathologic examination. One case of microscopic bilateral disease was not recognized by the surgeon. Seventeen patients were thought to have unilateral multicentric disease. Fifteen of these cases were confirmed by microscopy and an additional seven cases were documented to have secondary foci. It is obvious from this study that most disease that is called microscopic disease is actually palpable. A review of the literature confirms this. It was very unlikely for a patient who did not have unilateral multicentric disease to have a contralateral focus of carcinoma. The incidence of bilateral disease was 32%, and the incidence of multicentric disease was 50%; the surgeon was very accurate in assessing this. We believe that surgeons who advocate lobectomy as the primary treatment for thyroid cancer are recognizing grossly detectable disease in a significant number of patients and thus are doing total thyroidectomies in most patients with bilateral disease.

Adolescent↗

[An autopsy case of multicentric glioma of multiple histopathology].

An autopsy case is described of an 66-year-old man with multicentric glioma of multiple histopathology, i.e. protoplasmic astrocytoma and glioblastoma. Enhanced CT scan revealed three separate lesions in the right cerebral hemisphere, pons, and cerebellar vermis. Initial diagnosis by CT included metastatic and primary brain tumor, multiple abscess, fungal infection, parasites, tuberculoma, and so on. Biopsy of the right frontal mass revealed astrocytoma grade-2. An autopsy revealed gelatinous, clear marginal mass in the right frontal, parietooccipital and cerebellar vermis; an opaque marginal mass with necrosis in dorsal pons was found. At microscopic examination, the right frontal tumor exhibited continuity with both the paraventricular and the right parietooccipital tumor. The right cerebral hemisphere and cerebellar vermis tumors showed protoplasmic astrocytoma; the dorsal pons tumor showed glioblastoma. CSF examination revealed no tumor cells. Tumor invasion of the internal capsule and the meninges was also not found. Accordingly, we diagnosed as multicentric astrocytoma of multiple histopathology. Only 11 case reports of multicentric glioma were recorded in Japan; only one of which was of multiple histopathology. Worldwide, only 7 case reports of multicentric glioma of multiple histopathology were recorded; this is the first case of protoplasmic astrocytoma and glioblastoma. Seen in terms of pathogenesis of multicentric glioma, this case is thought to be very interesting.

Astrocytoma↗

Investigation of resected multinodular hepatocellular carcinoma: assessment of unicentric or multicentric genesis from histological and prognostic viewpoint.

OBJECTIVES: Multicentricity of hepatocellular carcinoma (HCC) is attracting a great deal of attention at present. However, few studies have focused on the prognostic comparison between unicentric and multicentric multinodular HCCs. The aim of this study is the reevaluation of histologic criteria of multicentric HCC and a prognostic comparison between the two groups mentioned above. METHODS: Forty-nine cases with intrahepatic multiple nodules of HCC, by gross examination, among 184 consecutive resected HCCs were examined clinicopathologically. These cases were divided into three groups: group A, cases suggestive of multicentric genesis; group B, unicentric cases; and group C, indeterminate cases. Histopathological characteristics and the cumulative survival rates were compared among these groups. RESULTS: Five cases were categorized as group A, 36 cases as group B, and eight cases as group C. Nodules in group A were smaller than 2 cm in diameter, situated discretely and well differentiated, and with neither vascular nor capsular invasion. Most of the nodules lacked a tumor capsule and had an irregular border. In the 36 cases of group B, all main tumors had vascular and/or capsular invasion. The cellularity index was almost the same in all groups. The cumulative survival rate of group A was better than that of group B or group C. CONCLUSIONS: Small multiple nodules of well-differentiated hepatocellular carcinoma without vascular and capsular invasion might be multicentric, and these early detections and operations could result in a fairly good prognosis, despite the multiple HCC nodules.

Aged↗

[Helical CT of the breast: detection of intraductal spread and multicentricity of breast cancer].

PURPOSE: This study was performed to evaluate the clinical utility of postcontrast helical CT (HCT) scan for the detection of intraductal spread (DS) and multicentricity of breast cancer. MATERIALS AND METHODS: DS and multicentricity in 84 patients with invasive ductal carcinoma were evaluated by preoperative postcontrast HCT. The HCT protocol of 3-mm section width and 3 mm/sec table speed was used with the patients in a supine position. Scanning started 70sec after beginning the intravenous injection of 90 ml (27 gI) of contrast material at the rate of 1.5 ml/sec. The three-dimensional images were displayed. RESULTS: Eighty-four of 84 main tumors (100%) were shown as enhanced masses by postcontrast HCT. The sensitivity and specificity of HCT for the detection of DS and multicentricity were 60.0% (18/30) and 88.9% (48/54), and 88.9% (16/18) and 90.9% (60/66), respectively. When DS and multicentric lesions were combined, the sensitivity and the specificity were 76.3% (29/38) and 89.1% (41/46), respectively. CONCLUSION: HCT of the breast is effective in detecting DS and multicentric lesions of breast cancer and might be useful in helping surgeons to successfully perform breast-conserving surgery.

Adult↗

Magnetic resonance imaging and its role in the diagnosis of multicentric breast cancer.

Multicentric breast cancer is one of the most important contraindications for breast conserving therapy. While the sensitivity of mammography decreases in the dense breast, the present study was designed to assess the efficacy of contrast-enhanced magnetic resonance imaging (MRI) for the diagnosis of multicentric breast cancer compared to clinical examination, mammography and sonography. In 38 of 46 patients who underwent modified radical mastectomy, multicentric breast cancer was found histologically according to the definition of Holland et al The sensitivity for the diagnosis of multicentricity in breast cancer was as follows: palpation (47%), mammography (66%), sonography (79%) and MRI (89%). While MRI had the highest sensitivity, the specificity was the lowest showing 8 false positive enhancements (proliferative fibroadenomas, fibrocystic disease and papilloma). Compared to the other methods, MRI assessed the multicentric extent of breast cancer with the highest sensitivity which appears most important in radiodense breasts when breast conserving therapy is planned.

Breast Neoplasms↗

The management of unicentric and multicentric Castleman's disease: a report of 16 cases and a review of the literature.

BACKGROUND: Castleman's disease (CD), or angiofollicular lymph node hyperplasia, creates both diagnostic and therapeutic dilemmas for most physicians. For patients with this rare and poorly understood disease, the optimal therapy is unknown. The authors report their experience during the years 1986-1997 with this uncommon clinicopathologic entity. METHODS: Sixteen patients with a histologic diagnosis of CD were identified in the pathology database. Unicentric disease was defined as a solitary mass. Multicentric disease compromised patients with widespread lymphadenectomy. Clinical, radiologic, and laboratory data were analyzed to evaluate treatment response. RESULTS: The study group consisted of 16 patients classified into 3 clinicopathologic groups: hyaline-vascular, plasma cell, and "mixed." Of those patients who underwent complete surgical excision of a unicentric hyaline-vascular CD mass (n = 8), all remain symptom free without clinical or radiographic recurrence. Two patients remain asymptomatic following partial resection or radiation therapy for an unresectable unicentric hyaline-vascular CD mass. Two patients with multicentric hyaline-vascular CD are currently in complete remission following adjuvant therapy. Multicentric plasma cell CD was present in a single patient. This patient (who underwent surgical and systemic therapy) died of disease within 4 months of presentation. Three patients with unicentric hyaline-vascular/plasma cell-CD remain symptom free following either complete resection or observation. CONCLUSIONS: The authors recommend surgical resection for patients with the unicentric variant of CD. Surgical removal of a unicentric mass of hyaline-vascular or hyaline-vascular/plasma cell type is curative. Partial resection, radiotherapy, or observation alone may avoid the need for excessively aggressive therapy. Patients with multicentric disease, either hyaline-vascular or plasma cell type, do not benefit from surgical management and should be candidates for multimodality therapy, the nature of which has yet to be defined.

Adult↗

Differentiation of multicentric origin from intra-organ metastatic spread of hepatocellular carcinomas by comparative genomic hybridization.

In hepatocellular carcinoma (HCC), multifocal growth may be due to intrahepatic metastatic spread or to the multicentric origin of clonal neoplasms. Although this issue is of potential clinical and prognostic importance, reliable differentiation cannot be achieved using clinical or morphological criteria alone. In this study, comparative genomic hybridization (CGH) was used to differentiate between metastatic spread and multicentric growth in two cases of HCC. In the first case, six carcinoma nodules were examined. The affected chromosomes and their pattern of aberrations were almost identical for all six nodules. In addition to aberrations of chromosomes 1, 4, 9, and 13, further aberrations were observed for chromosomes 2, 5, 7, and 17, which are less typical for HCC. These findings were seen as indicative of metastatic spread of the HCC. In the second case, 75% (3/4) of the nodules showed comparable aberration patterns involving chromosomes 1, 4, 8, 13, and 17, together with a number of further aberrations also not frequently seen in HCC including chromosomes 5, 7, 10, 12, 14, and 18. Chromosomes 4, 5, 8, 10, and 12 were also altered in the fourth nodule examined for this case, but they exhibited a unique aberration pattern. Additionally, gain of chromosome 15q was seen in only this fourth nodule. In the two cases examined, metastatic spread and multicentric origin of HCC could be differentiated by different patterns of karyotypic change. The CGH results were confirmed by fluorescence in situ hybridization (FISH). In conclusion, CGH facilitates the differentiation of multicentric growth from metastatic spread in HCC and appears to be superior to techniques previously used to resolve this clinically important diagnostic problem.

Adult↗

Multifocal vulvar intraepithelial neoplasia grade III and multicentric lower genital tract neoplasia is associated with transcriptionally active human papillomavirus.

BACKGROUND: The incidence of vulvar intraepithelial neoplasia Grade III (VIN III) is increasing and is diagnosed at a younger age than previously. VIN III is often multifocal and frequently coexists with multicentric dysplastic lesions in the cervix and vagina. Warty-type VIN III more often has been found to contain human papillomavirus (HPV) DNA than basaloid-type VIN III: The authors performed HPV DNA polymerase chain reaction (PCR) analysis in 48 VIN III biopsies and reverse transcriptase (RT)-PCR in 8 HPV-16 DNA-positive multifocal VIN III biopsies to detect E6/E7 transcripts. METHODS: Human papillomavirus DNA detection and histologic analysis were performed on alternating slides of paraffin embedded biopsies. Polymerase chain reaction was performed with consensus primers, and HPV typing was performed by direct sequencing. Total RNA was isolated from frozen biopsies by centrifuging a guanidinium thiocyanate (GTC) lysate through a cesium chloride (CsCl) cushion. The RT reaction was performed using a 3' primer, located just downstream of the E7 stop codon, and the PCR reaction was performed using the same 3' primer and a 5' primer located just downstream of the E6 start codon. RESULTS: The mean age of the 48 patients was 37.7 years. Eighty-one percent had multifocal VIN III: Sixty-six percent had multicentric neoplasia. Forty-six percent of the biopsies were warty-type, 17% basaloid-type, 35% mixed-type and 2% differentiated-type. Ninety-two percent were HPV-positive and 83% contained HPV-16 DNA. Human papillomavirus DNA was more often present in multifocal VIN III lesions than in unifocal VIN III lesions and also more often in VIN III lesions coexisting with other dysplastic multicentric lesions than in unicentric VIN III lesions. Warty-type VIN III more often contained koilocytes than basaloid-type VIN III: A correlation between different morphologic forms of VIN III and the presence of HPV DNA was not found. Both types of VIN III often coexist in one lesion. In all the RT-PCRs, a 593-base-pair fragment was detected, corresponding to the expected length of the major E6*-E7 mRNA. CONCLUSIONS: The observed high prevalence of transcriptionally active HPV DNA associated with multifocal and multicentric dysplasia suggests a role of HPV in the pathogenesis of these lesions. A positive correlation between different morphologic forms of VIN III and the presence of HPV DNA was not found.

Adult↗

Genetic determinants of feline leukemia virus-induced multicentric lymphomas.

Three discrete forms of feline leukemia virus (FeLV)-associated lymphoma have been described clinically: (1) thymic, (2) alimentary, and (3) multicentric. The most common and best-characterized lymphomas are of T-cell origin, generally occurring in the thymus. These tumors typically contain mature T-cells, involve the activation of a distinctive set of proto-oncogenes, and contain FeLV proviruses whose long terminal repeat (LTR) sequences contain tandemly repeated enhancers. Previous studies of a small group of extrathymic, multicentric lymphomas implicated a different set of genetic determinants. The present study expands those observations by examining the lineage of origin, the involvement of proto-oncogenes, and the structure of LTR and env gene sequences in a set of 11 natural, extrathymic lymphomas of the multicentric type. A pattern of genetic events associated with FeLV-positive multicentric lymphomas emerges from this analysis that is clearly distinct from the pattern associated with thymic lymphomas. The tumors do not contain T-cells or B-cells, as evidenced by the germ line organization of TCR beta and IgH loci. Proto-oncogenes strongly implicated in T-cell lymphomagenesis are not involved in these tumors. Rather, a distinct set of proto-oncogenes may be involved. Most striking is the repeated occurrence of an FeLV isolate whose LTR and env gene bear unique sequence elements.

Amino Acid Sequence↗

Multicentricity and histopathological background features of familial breast cancers stratified by menopausal status.

BACKGROUND: We investigated histopathological background and multicentricity in patients with familial breast cancers (FBCs) in comparison with these features in patients with sporadic breast cancers (SBCs), stratifying patients by menopausal status. METHODS: We collected a consecutive series of 469 FBC patients and 3334 SBC patients treated at our hospital between 1965 and 1995. The following criteria were used to define FBC, regardless of the presence or absence of a family history of other cancer or the patient's past history of malignancies: (1) Three or more second-degree relatives had been affected by breast cancer; (2) two first-degree relatives had been affected by breast cancer, and either one of them was under 40 years of age and/or had had bilateral breast cancers. The presence or absence of background proliferative lesions (PL; ductal/lobular hyperplasia and/or adenosis) and the multicentricity of breast carcinomas in FBCs and SBCs were analyzed for each group. RESULTS: In premenopausal FBC patients, there was a non-significant trend towards a high frequency of multicentricity compared with findings in patients with SBCs overall (P = 0.087; odds ratio [OR], 1.43; 95% confidence interval [CI], 0.96-2.13). In premenopausal FBC patients, the frequency of background proliferative lesions with/or without fibroadenomas (FA) in the resected specimen was significantly higher than that in SBC patients overall (P = 0.001 for PL; OR, 1.47; 95% CI, 1.18-1.83; P < 0.001 for PL +/- FA; OR, 6.84; 95% CI, 4.93-9.49). With regard to the other clinicopathological factors examined, there were no significant differences between the two groups, except for the higher frequency of premenopausal patients among the FBC patients. CONCLUSION: These results indicate that premenopausal patients with FBCs had more proliferative lesions in the histopathological background and more multicentric breast cancers than premenopausal patients with SBCs.

Adult↗

Multicentric glioma with unusual clinical presentation.

Multiple glioma is a well-recognized but uncommon entity. They are grouped in two categories: multifocal and multicentric gliomas. Multifocal gliomas grow through dissemination along an established route, spreading through commissural pathways, CSF channels, or the blood or by local extension through satellite formation; at the opposite end of the spectrum, multicentric gliomas are widely separated lesions whose simultaneous presence cannot be attributed to any of the above pathways. Reports in the literature refer to single cases or small series of multicentric gliomas, almost always in adult patients, their occurrence in children being even less frequent. We report the case of a 12-year-old boy with multicentric glioma, atypical acute clinical onset and fast growth of three other tumors in 8 months, and then discuss the problems of diagnosis and therapy.

Brain Neoplasms↗

Recurrence of hepatocellular carcinoma: multicentric occurrence or intrahepatic metastasis? A viewpoint in terms of pathology.

Recurrence after successful surgical or nonsurgical treatment of hepatocellular carcinoma (HCC) is caused either by intrahepatic metastasis or by metachronously multicentric occurrence. Intrahepatic metastasis is a major cause of recurrence of advanced HCCs with varying degrees of vascular invasion, and multicentric occurrence is a frequent cause of recurrence in small HCCs with no obvious vascular invasion. It is estimated that at least 20% of small HCCs have a high probability of recurrence due to multicentric occurrence, based on the finding that adenomatous hyperplasia (AH) and/or atypical adenomatous hyperplasia (AAH), which are considered premalignant lesions, are found in the vicinity of resected small HCCs with liver cirrhosis. However, because neither AH nor AAH occur in HCC cases without liver cirrhosis, most recurrence of HCC in noncirrhotic liver is considered to be due to intrahepatic metastasis or to de novo hepatocarcinogenesis. In a survey of autopsy cases of liver cirrhosis with small HCC, smaller HCC nodules were found in other liver slices in 50% of cases, and it is estimated that approximately 50% of HCC is already multicentric in the early stage.

Carcinoma, Hepatocellular↗

The extent and multicentricity of high-grade prostatic intraepithelial neoplasia in clinically localized prostatic adenocarcinoma.

High-grade prostatic intraepithelial neoplasia (PIN) is considered the most likely precursor of invasive prostatic adenocarcinoma, and is characterized by cellular proliferations within preexisting ducts and glands with cytological changes mimicking cancer. The extent and multicentricity of this clinically important histopathologic lesion have not been fully defined. We sought to determine whether the extent and zonal distribution of PIN are related to prostate cancer. A total of 195 whole-mounted radical prostatectomy specimens were evaluated. All patients had clinically localized cancer, and none had received preoperative therapy. The zonal location and multicentricity of PIN were recorded, and the volume of PIN was measured using a grid-counting method according to pattern (tufting, micropapillary, cribriform, and flat) and spatial proximity to cancer (less than or equal to 2 mm from cancer, and greater than 2 mm from cancer). The results were correlated with patient age, prostate volume, cancer volume, pathological stage, and Gleason grade. High-grade PIN was identified in 86% of cases, usually with multiple architectural patterns of PIN in each positive case: tufting (97% of cases), micropapillary (66% of cases), cribriform (19% of cases), and flat (21% of cases). The mean volume of PIN was 1.32 cm3 (standard error [SE], 0.10; range, 0 to 8.12 cm3), and was greater for PIN within 2 mm of cancer (mean, 1.0 cm3) than for PIN more than 2 mm from cancer (mean, 0.3 cm3). PIN was usually multicentric (64.5% of cases) and located in the nontransition zone (63%) or all zones (36%) of the prostate. There was a positive correlation of total volume of PIN and volume of cancer, but this correlation was significant only for PIN within 2 mm of cancer. The volume of PIN was positively correlated with age, pathological stage, and Gleason score; most of these positive correlations were caused by PIN within 2 mm of cancer rather than that greater than 2 mm from cancer. Our results indicate that the extent and zonal distribution of high-grade PIN and carcinoma are strongly associated, and that PIN is frequently multicentric. This supports the hypothesis that PIN is a premalignant lesion.

Adenocarcinoma↗