Epithelioid angiomyolipoma: a pathological entity discovered in Verona with the endorsement of Doctor Rosai.

In this manuscript, we summarize the main features of angiomyolipoma highlighting the recognition of epithelioid angiomyolipoma and the discovery of immunohistochemical expression of HMB45 in a group of tumors that now are referred to as as PEComas. In this scenario, Dr. Rosai believed in our intuition, demonstrating his intellectual honesty and motivated us with his experience ("when a tumor seems malignant it is malignant") and enthusiasm for the new entities ("in Verona, you use HMB45 instead of H&E"). He really pushed the improvement of the knowledge in this field.

Angiomyolipoma of the kidney: from simple hamartoma to complex tumour.

Angiomyolipoma is the most common mesenchymal tumour of the kidney, even if for a long time it has been viewed as a hamartoma rather than a neoplasm. It belongs to a family of neoplasms, named PEComa, characterised by the constant presence of perivascular epithelioid cells that co-express smooth muscle and melanogenesis markers. Angiomyolipoma can occur in patients with tuberous sclerosis, a hereditary syndrome due to the alteration of TSC1 or TSC2 genes, or sporadically. Angiomyolipoma and its variants are indolent tumours; however, some epithelioid angiomyolipomas/pure epithelioid PEComas are aggressive, and criteria for malignancy have been proposed to identify those cases. Although typical angiomyolipoma is a straightforward diagnosis, pathologists should be aware of the wide morphological spectrum of its variants which could be tricky in routine clinical practice and could require immunohistochemical analysis for resolution. The differential diagnosis may range from an inflammatory process (for instance xanthogranulomatous pyelonephritis) to the most common renal cancers and sarcomas. The immunoexpression of melanogenesis markers (HMB45 and Melan-A) and cathepsin K is extremely helpful in the majority of cases. Recently, a subset of epithelioid angiomyolipoma/pure epithelioid PEComa harbouring TFE3 gene fusions has been described, raising questions about its relationship with the family of perivascular epithelioid cell tumour. The activation of the mTOR pathway due to genetic alterations of tuberous sclerosis complex in TSC1 or TSC2 genes in angiomyolipoma has also been reported as well as the subsequent therapeutic implications.

HPV-related papillary squamous cell carcinoma of the tonsil during treatment with fingolimod.

Fingolimod is a commonly used treatment for highly active relapsing-remitting multiple sclerosis (MS). We describe the case of a 50-year old man on fingolimod since 2011 who presented, in April 2017, with a voluminous swelling of the left tonsil. A left tonsillectomy was performed, and histological exam disclosed a papillary squamous cell carcinoma of the palatine tonsil, with an in situ hybridization positive for human papillomavirus (HPV)-16 DNA. Neither lymph nodes involvement nor other metastases were detected. Fingolimod was stopped as a precautionary measure in May 2017, and the patient currently continues his follow up at our Department. Immunocompromised patients are at risk for developing HPV-related malignancies probably in light of the suppression of T-cell immunity, therefore an increased risk for HPV activation in MS patients treated with disease modifying therapies (DMTs) characterized by a more pronounced immunosuppressant activity cannot be excluded. Given the absence of studies on larger cohorts of MS patients exposed to DMTs, additional monitoring for HPV infection during fingolimod treatment is not currently recommended. However, vigilance for this possible association is warranted.

Cathepsin K expression in clear cell "sugar" tumor (PEComa) of the lung.

Clear cell "sugar" tumor is a rare benign neoplasm arising in the lung, considered as a part of the PEComa family. As PEComas of other sites, this tumor expresses melanocytic markers such as HMB45 and Melan-A. Despite cathepsin K, MITF and CD68 staining are known to be positive in a large number of PEComas and TFE3 rearrangement has been reported in a subset of PEComas, no data is available regarding the expression of these markers and the occurrence of TFE3 and TFEB rearrangement in clear cell "sugar" tumor of the lung. We have investigated the immunolabeling of cathepsin K, MITF, and CD68 in five cases of clear cell "sugar" tumor. Moreover, we have also sought the presence of TFE3 and TFEB rearrangement by fluorescence in situ hybridization (FISH) assay. In all tumors, strong immunoreactivity of cathepsin K and CD68 (PG-M1 and KP1 clone) was demonstrated, whereas none of them labeled for MITF staining and showed TFE3 or TFEB rearrangement. These findings widen the immunohistochemical profile of clear cell "sugar" tumor providing useful new markers for challenging cases. The expression of lysosomal markers, such as cathepsin K and CD68, strengthens the hypothesis that this tumor is part of the PEComa family.

PEComas of the kidney and of the genitourinary tract.

PEComas are mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells that are characterized by the coexpression of muscle and melanogenetic markers. This group of lesions includes angiomyolipoma, clear cell "sugar" tumor of the lung and extrapulmonary sites, lymphangioleiomyomatosis, clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres, and rare clear cell tumors of other anatomical sites. In the genitourinary tract, PEComas have been described in the kidney, bladder, prostate, testis, and urethra. Although most PEComas behave as benign tumors, some are potentially malignant, and criteria for malignancy have been suggested for both and renal and extrarenal lesions. Recently, the expression of cathepsin K has been demonstrated in a large number of PEComas and has been proposed as a relatively specific marker to distinguish these proliferations from the majority of human cancers. In addition, a distinctive subset of PEComas harboring TFE3 gene fusions has been reported, giving rise to a possible relationship between them and MiTF/TFE family translocation renal cell carcinomas. The genetic alterations of tuberous sclerosis complex that promote activation of the mTOR pathway have been identified in PEComas. Therapy with mTORC1 inhibitors has been shown to be effective in some cases.

Healing of fresh extraction sockets filled with bioactive glass particles: histological findings in humans.

PURPOSE: The aim of the present study was to histologically evaluate fresh human sockets filled with bioactive glass after 6 months of healing. MATERIALS AND METHODS: In 13 patients, 32 single extraction sites in the anterior area underwent socket ridge preservation procedure (RPP) with a bioactive glass (BioRestore™, Inion Oy, Tampere, Finland). At implant installation, 22 bone cores were trephined out and processed for histomorphometric and immunohistochemical analysis. RESULTS: Newly formed immature bone around residual particles of bioactive glass was found in all 22 biopsies. The histomorphometry of the amount of bone, provisional matrix, and residual graft returned a mean ± SD value of 54 ± 31%, 37.9 ± 25.6%, and 8.1 ± 7.8, respectively, 6 months after RPP. CONCLUSION: The use of this grafting material in fresh extraction sockets appears to delay the healing processes of the alveolar bone; therefore, its indication as a material for RPP when implant placement is considered within 6 months after extraction should be revised.

Cathepsin K expression in the spectrum of perivascular epithelioid cell (PEC) lesions of the kidney.

The perivascular epithelioid cell (PEC) is a unique cell type coexpressing contractile proteins (mainly α-smooth muscle actin), melanocytic markers, including microphthalmia-associated transcription factor (MITF), and estrogen and progesterone receptors. It is constantly present in a group of tumors called PEComas. Renal PEComas include the common angiomyolipoma as well as less common lesions such as microscopic angiomyolipoma, intraglomerular lesions, angiomyolipoma with epithelial cysts, epithelioid angiomyolipoma, oncocytoma-like angiomyolipoma and lymphangioleiomyomatosis of the renal sinus. It has been demonstrated that most of these lesions are determined by mutations affecting genes of the tuberous sclerosis complex, tuberous sclerosis 1 (TSC1) and tuberous sclerosis 2 (TSC2), with eventual deregulation of the RHEB/MTOR/RPS6KB2 pathway, and it has been observed that some PEComas regressed during sirolimus therapy, an MTOR inhibitor. Recently, overexpression of MITF has been related to the expression of the papain-like cysteine protease cathepsin K in osteoclasts where it has inhibited MTOR. The aim of this study is to evaluate cathepsin K immunohistochemically in the entire spectrum of PEComa lesions in the kidney. The study population consisted of 84 renal PEComa lesions, including 5 composed predominantly of fat (lipoma-like angiomyolipoma), 15 almost exclusively composed of spindle-shaped smooth muscle cells (leiomyoma-like angiomyolipoma) and 31 common angiomyolipomas composed of a mixture of fat, spindle and epithelioid smooth muscle cells, and abnormal thick-walled blood vessels, 15 microscopic angiomyolipomas, 5 intraglomerular lesions, 2 oncocytoma-like angiomyolipomas, 8 epithelioid angiomyolipomas, 2 angiomyolipomas with epithelial cysts and 1 example of lymphangioleiomyomatosis of the renal sinus. In all of the renal PEComas, cathepsin K was found to be constantly and strongly expressed and seems to be a more powerful marker than other commonly used markers for their identification, especially to confirm the diagnosis on needle biopsies.

Differential expression of cathepsin K in neoplasms harboring TFE3 gene fusions.

Cathepsin K is a protease whose expression is driven by microphthalmia transcription factor (MITF) in osteoclasts. TFE3 and TFEB are members of the same transcription factor subfamily as MITF and all three have overlapping transcriptional targets. We have shown that all t(6;11) renal cell carcinomas, which harbor an Alpha-TFEB gene fusion, as well as a subset of the Xp11 translocation renal carcinomas, which harbor various TFE3 gene fusions, express cathepsin K, while no other common renal carcinoma does. We have hypothesized that overexpression of TFEB or certain TFE3 fusion proteins function like MITF in these neoplasms, and thus activate cathepsin K expression. However, the expression of cathepsin K in specific genetic subtypes of Xp11 translocation carcinomas, as well as alveolar soft part sarcoma, which harbors the same ASPSCR1-TFE3 gene fusion as some Xp11 translocation carcinomas, has not been addressed. We performed immunohistochemistry for cathepsin K on 14 genetically confirmed t(X;1)(p11;q21) carcinomas, harboring the PRCC-TFE3 gene fusion; eight genetically confirmed t(X;17)(p11;q25) carcinomas, harboring the ASPSCR1-TFE3 gene fusion; and 18 alveolar soft part sarcomas (12 genetically confirmed), harboring the identical ASPSCR1-TFE3 gene fusion. All 18 alveolar soft part sarcomas expressed cathepsin K. In contrast, all eight ASPSCR1-TFE3 carcinomas were completely negative for cathepsin K. However, 12 of 14 PRCC-TFE3 carcinomas expressed cathepsin K. Expression of cathepsin K distinguishes alveolar soft part sarcoma from the ASPSCR1-TFE3 carcinoma, harboring the same gene fusion. The latter can be useful diagnostically, especially when alveolar soft part sarcoma presents in an unusual site (such as bone) or with clear cell morphology, which raises the differential diagnosis of metastatic ASPSCR1-TFE3 renal cell carcinoma. The difference in expression of cathepsin K between the PRCC-TFE3 and ASPSCR1-TFE3 carcinomas, together with the observed clinical differences between these subtypes of Xp11 translocation carcinomas, suggests the possibility of functional differences between these two related fusion proteins.

Pure epithelioid PEComas (so-called epithelioid angiomyolipoma) of the kidney: A clinicopathologic study of 41 cases: detailed assessment of morphology and risk stratification.

Epithelioid angiomyolipomas (perivascular epithelioid cell tumors) of the kidney are defined as potentially malignant mesenchymal lesions that are closely related to classic angiomyolipoma. Although approximately 120 cases are published, mostly as case reports with variably used diagnostic criteria, the pathologic prognostic predictors of outcome are unknown. We analyzed the clinicopathologic parameters in a large series of 41 cases of pure epithelioid angiomyolipomas of the kidney, which we designate as pure (monotypic) epithelioid PEComas to contrast them from classic angiomyolipomas that are regarded by some as PEComas. We use the terminology "pure" to separate these cases from those that may have variable epithelioid components. The mean age of the patients was 40.7 years (range, 14 to 68 y). The male-to-female ratio was 1:1. Seventy-nine percent of patients were symptomatic at presentation with metastatic disease at onset in 12 cases. Follow-up and/or disease progression information were available for 33 of 41 cases (mean, 44.5 mo and median, 24.5 mo; range, 4 to 240); 9 patients had a history of associated tuberous sclerosis. Recurrence and metastasis were seen in 17% and 49% of patients; 33% of patients died of disease. Lymph node involvement was seen in 24% of patients; the liver (63%), lung (25%), and mesentery (18.8%) were the most common metastatic sites. Clinicopathologic parameters associated with disease progression (recurrence, metastasis, or death due to disease) in univariate analysis included associated tuberous sclerosis complex or concurrent angiomyolipoma (any metastasis, P=0.046), necrosis (metastasis at diagnosis, P=0.012), tumor size >7 cm (progression, P=0.021), extrarenal extension and/or renal vein involvement (progression, P=0.023), and carcinoma-like growth pattern (progression, P=0.040) (the 5 adverse prognostic parameters for pure epithelioid PEComas). Tumors with <2 adverse prognostic parameters (13 cases) were considered to be low risk for progression tumor, with 15% having disease progression. Tumors with 2 to 3 adverse prognostic parameters (14 cases) were considered to be "intermediate risk," with 64% having disease progression. Tumors with more than 4 or more adverse prognostic parameters (6 cases) were considered to be high risk, with all patients having disease progression. Of tumors with 3 or more adverse prognostic parameters, 80% had disease progression. An exact logistic regression analytic model showed that only carcinoma-like growth pattern and extrarenal extension and/or renal vein involvement were significant predictors of outcome (P=0.009 and 0.033, respectively). Our data of a large series with uniform definitional criteria confirm the malignant potential for pure epithelioid PEComas and provide adverse prognostic parameters for risk stratification in these patients.

Molecular pathology of lymphangioleiomyomatosis and other perivascular epithelioid cell tumors.

CONTEXT: Lymphangioleiomyomatosis (LAM) is a cystic lung disease that can be included in the wide group of proliferative lesions named PEComas (perivascular epithelioid cell tumors). These proliferative tumors are characterized by the coexpression of myogenic and melanogenesis-related markers. In all these lesions, genetic alterations related to the tuberous sclerosis complex (TSC) have been demonstrated. Striking improvements in the understanding of the genetic basis of this autosomal dominant genetic disease are coupled to the understanding of the mechanisms that link the loss of TSC1 (9q34) or TSC2 (16p13.3) genes with the regulation of the Rheb/m-TOR/p70S6K pathway. These data have opened a new era in the comprehension of the pathogenesis of LAM and have also suggested new therapeutic strategies for this potentially lethal disease. OBJECTIVE: To present and discuss the pathologic and molecular features of LAM within the spectrum of PEComas, providing a rational approach to their diagnosis. DATA SOURCES: The published literature and personal experience. CONCLUSIONS: The inclusion of LAM within the PEComa category is supported by a variety of biologic data and can significantly help in providing a comprehensive view of this interesting and clinically relevant group of lesions. The demonstration of molecular alterations of the mTOR pathway in LAM and other PEComas represents a rational basis for innovative therapeutic approaches with inhibitors of mTOR signaling.

Cathepsin-k expression in pulmonary lymphangioleiomyomatosis.

Lymphangioleiomyomatosis is a rare and progressive lung cystic disease, caused by the infiltration of lung parenchyma by mesenchymal cells characterized by co-expression of contractile proteins and melanocytic markers. The pathogenesis of lymphangioleiomyomatosis is determined by mutations affecting tuberous sclerosis complex (TSC) genes, with eventual deregulation of the Rheb/mTOR/p70S6K pathway, and the potential therapeutic activity of mTOR inhibitors is currently under investigation. To better understand the molecular mechanisms involved in the pathogenesis of lymphangioleiomyomatosis, we investigated the expression of cathepsin-k (a papain-like cysteine protease with high matrix-degrading activity). The rationale of this choice was based on the recent demonstration that mTOR inhibitors can regulate major functional activities of osteoclasts, including the expression of cathepsin-k. The immunohistochemical study included 12 cases of lymphangioleiomyomatosis. Twelve angiomyolipomas and several lung diseases (sarcoidosis, organizing pneumonia, usual interstitial pneumonia, emphysema) were investigated as controls. In all lymphangioleiomyomatosis cases, strong cathepsin-k immunoreactivity was demonstrated, restricted to lymphangioleiomyomatosis cells. Similar expression levels were observed in renal angiomyolipomas. These observations extend the knowledge regarding the immunophenotypic profile of lymphangioleiomyomatosis cells, and provide a useful new marker for diagnosis in difficult cases (eg, in small transbronchial biopsies). The strong expression of such a potent papain-like cysteine protease in lymphangioleiomyomatosis cells can significantly contribute to the progressive remodelling of lung parenchyma observed in this deadly disease, with eventual formation of lung cysts. It is possible to speculate that mTOR inhibitors may exert part of their action by limiting the destructive remodelling of lung structure.

PEComas: the past, the present and the future.

The perivascular epithelioid cell (PEC) is a cell type constantly present in a group of tumors called PEComas. PEC expresses myogenic and melanocytic markers, such as HMB45 and actin. Recently, recurrent chromosomal alterations have been demonstrated in PEC. At present, PEComa is a widely accepted entity. In the past 10 years, the use of this term has allowed to report and describe numerous cases permitting to start highlighting the biology of this group of lesions. PEComas are related to the genetic alterations of tuberous sclerosis complex (TSC), an autosomal dominant genetic disease due to losses of TSC1 (9q34) or TSC2 (16p13.3) genes which seem to have a role in the regulation of the Rheb/mTOR/p70S6K pathway. There are some open questions about PEComas regarding its histogenesis, the definition of epithelioid angiomyolipoma and the identification of the histological criteria of malignancy. An innovative therapeutic trial using rapamycin is under way for tumors occurring in TSC such as renal angiomyolipoma and lymphangioleiomyomatosis. Its success could provide the rationale for the use of the same drug in other lesions composed of PECs, especially in the malignant ones.

Diagnostic utility of S100A1 expression in renal cell neoplasms: an immunohistochemical and quantitative RT-PCR study.

S100A1 is a calcium-binding protein, which has been recently found in renal cell neoplasms. We evaluated the diagnostic utility of immunohistochemical detection of S100A1 in 164 renal cell neoplasms. Forty-one clear cell, 32 papillary, and 51 chromophobe renal cell carcinomas, and 40 oncocytomas, 164 samples of normal renal parenchyma adjacent to the tumors and 13 fetal kidneys were analyzed. The levels of S100A1 mRNA detected by quantitative RT-PCR analysis of frozen tissues from seven clear cell, five papillary, and six chromophobe renal cell carcinomas, four oncocytomas, and nine samples of normal renal tissues adjacent to neoplasms were compared with the immunohistochemical detection of protein expression. Clear cell and papillary renal cell carcinomas showed positive reactions for S100A1 in 30 out of 41 tumors (73%) and in 30 out of 32 (94%) tumors, respectively. Thirty-seven renal oncocytomas out of 40 (93%) were positive for S100A1, whereas 48 of 51 (94%) chromophobe renal cell carcinomas were negative. S100A1 protein was detected in all samples of unaffected and fetal kidneys. S100A1 mRNA was detected by RT-PCR in all normal kidneys and renal cell neoplasms, although at very different levels. Statistical analyses comparing the different expression of S100A1 in clear cell and chromophobe renal cell carcinomas observed by immunohistochemical and RT-PCR methods showed significant values (P<0.001), such as when comparing by both techniques the different levels of S100A1 expression in chromophobe renal cell carcinomas and oncocytomas (P<0.001). Our study shows that S100A1 protein is expressed in oncocytomas, clear cell and papillary renal cell carcinomas but not in chromophobe renal cell carcinomas. Its immunodetection is potentially useful for the differential diagnosis between chromophobe renal cell carcinoma and oncocytoma. Further, S100A1 protein expression is constantly detected in the normal parenchyma of the adult and fetal kidney.

Role of molecular markers in diagnosis and prognosis of renal cell carcinoma.

It has been demonstrated that different renal cell neoplasms have characteristic morphologic and genetic features. Histologic subtyping of renal epithelial neoplasms has been shown to be of prognostic value; therefore they must be correctly classified. Although adequate sampling and a good understanding of the morphologic features usually minimize diagnostic errors, the use of immunohistochemical and chromosomal analysis on formalin-fixed, paraffin-embedded tissues can be necessary. These techniques can facilitate diagnosis on small biopsies, which are increasingly obtained from renal masses. An immunohistochemical panel including CD10, parvalbumin, AMACR, CK7 and S100A1 seems the most promising; fluorescence in situ hybridization analysis using centromeric probes to evaluate the gains and losses of the chromosomes can be helpful in selected cases. A wide variety of molecular markers have been examined, but further research is required to prove their value as prognostic tools.

Chromosomal gains in the sarcomatoid transformation of chromophobe renal cell carcinoma.

The hallmark of chromophobe renal cell carcinoma is multiple chromosomal losses from among chromosomes 1, 2, 6, 10 and 17. Chromophobe renal cell carcinoma with distant metastases or sarcomatoid transformation are uncommon and little is known about their chromosomal abnormalities. We collected six sarcomatoid chromophobe renal cell carcinomas and three primary chromophobe renal cell carcinomas with distant metastases. A cytogenetic analysis by fluorescent in situ hybridization on paraffin-embedded tissue was performed using centromeric probes for chromosomes 1, 2, 6, 10 and 17. We found more than one signal in four of six (66%) sarcomatoid chromophobe renal cell carcinomas, in both sarcomatoid and adjacent epithelial components. Both primary chromophobe renal cell carcinomas and matched metastases showed single signals for all chromosomes studied in two cases and no abnormalities in the remaining case. We concluded that: (1) both epithelial and sarcomatoid components of sarcomatoid chromophobe renal cell carcinoma show different genetic abnormalities from those characteristic of chromophobe renal cell carcinoma; (2) sarcomatoid chromophobe renal cell carcinomas frequently have multiple gains (polysomy) of chromosomes 1, 2, 6, 10 and 17; (3) distant metastases show the same genetic patterns, usually chromosomal losses (monosomy), found in the primary tumors.

Perivascular epithelioid cell tumor (PEComa) in the genitourinary tract.

Perivascular epithelioid cell tumors (PEComas) are mesenchymal tumors composed of histologically, immunohistochemically, ultrastructurally, and genetically distinctive cells. PEComas have been described in different organs and are considered ubiquitous tumors. In this review we discuss recent informations related to PEComas in the genitourinary tract.

Prognostic role of the histologic subtypes of renal cell carcinoma after slide revision.

OBJECTIVES: To evaluate concordance, using the kappa statistic, between tumour histotypes assigned at initial diagnosis and those after slide revision, and to assess the independent predictive value of reviewed tumour histotype. MATERIALS AND METHODS: We analysed records of 491 patients who had undergone partial or radical nephrectomy for renal cell carcinoma (RCC) in our department from 1986 to 2000. Pathologic slides were reviewed by one uropathologist blinded to original diagnoses and follow-up data, who reassigned histologic subtype and nuclear grades. RESULTS: Concordance between original and reviewed histotypes was substantial (kappa = 0.52). Data were affected by the year of initial diagnosis: Concordance was moderate (kappa = 0.43) in patients treated from 1986 to 1997 and substantial (kappa = 0.73) in those observed thereafter. The original histotype did not stratify the cancer-related outcome. According to the reviewed histotypes, the 5-year cancer-specific survival probabilities of conventional, papillary and chromophobe RCC patients were 81.3%, 90.1% and 100%, respectively (p = 0.009). Patients with conventional RCC showed significantly lower cancer-specific survival than those with papillary or chromophobe RCC, even in the cases with locally advanced (p = 0.04) or high-grade (p = 0.02) neoplasms. The reviewed histologic subtype was not an independent prediction of cancer-specific survival on multivariate analysis. CONCLUSION: Concordance between histologic subtype assigned before 1997 and after slide revision was only moderate. In univariate analysis, reviewed tumour histotype stratified cancer-related outcome, but the data of multivariate analysis were strongly influenced by the prevalent number of conventional RCC.

External validation of the Mayo Clinic Stage, Size, Grade and Necrosis (SSIGN) score to predict cancer specific survival using a European series of conventional renal cell carcinoma.

PURPOSE: We validated the Mayo Clinic SSIGN score in an independent European sample of patients who were surgically treated for conventional RCC. MATERIALS AND METHODS: In our kidney cancer database we identified 388 patients who were treated with radical or partial nephrectomy for conventional RCC between 1986 and 2000. Associations of the pathological features studied with death from RCC were evaluated using the log rank test and Cox proportional hazards regression model. The predictive ability of competing models was evaluated using the c index. RESULTS: Median followup in the 290 patients who were alive at last followup was 5 years (range 5 months to 17 years). The estimated cancer specific survival rate 5 years following surgery was 81.3%. All features that comprise the SSIGN score except tumor size were significantly associated with death from RCC in a multivariate setting, resulting in a c index of 0.90. The median SSIGN score in the 388 patients studied was 3 (range 0 to 15). The c index in a model containing the clear cell SSIGN score was 0.88. Five-year cancer specific survival rates in patients with a score of 0 to 2, 3 to 4, 5 to 6, 7 to 9 and 10 or more were 100.0%, 90.5%, 63.6%, 46.8% and 0%, respectively. CONCLUSIONS: We provide the first external validation of the Mayo Clinic SSIGN score for conventional RCC. This simple algorithm resulted in a high degree of prognostic accuracy.

Needle core length is a quality indicator of systematic transperineal prostate biopsy.

OBJECTIVE: To analyse the length of needle cores sampled as a quality indicator in systematic transperineal prostate biopsy. We assessed the correlation of core length with the other clinical and topographic parameters. MATERIAL AND METHODS: We prospectively evaluated data from 509 consecutive patients who underwent a first set of transrectal ultrasound-guided transperineal prostate biopsy for suspected prostate cancer. Fourteen cores were sampled from each patient. Needle cores were stretched and placed in tissue cassettes between two nylon meshes according to the pre-embedding methods of prostate needle biopsy specimens. For single biopsy core, the measurement of length (in millimetres) and any percentage of cancer in the biopsy specimen were reported. RESULTS: The mean length of 7,126 analysed cores was 14.14+/-4.35mm. All cores were longer than 10mm. The mean length of needle cores sampled did not correlate with patient age, total prostate-specific antigen value, digital rectal examination, and prostate volume. The whole mean length of the six samples from the peripheral zone of the right lobe was higher than the mean corresponding value of the six samples from the left lobe peripheral zone (p<0.001). The transperineal approach allows a greater sampling of the prostate apex than of the midgland and prostate base (p<0.001). CONCLUSIONS: The length of the needle cores sampled during transperineal prostate biopsy fulfils the parameters of quality required by pathologists for an appropriate evaluation of the biopsy specimen.

The potential impact of prostate volume in the planning of optimal number of cores in the systematic transperineal prostate biopsy.

OBJECTIVES: We compared the detection rates of different transperineal prostate biopsy protocols with the aim to optimize the number of cores to sample according to prostate volume. MATERIAL AND METHODS: From October 2002 to October 2004 we evaluated 480 consecutive patients with PSA between 2.5 and 20 ng/ml undergoing the first set of prostate biopsy. All patients underwent a 14-core TRUS-guided transperineal prostate biopsy, including 12 cores in the peripheral and two in the transitional zone. The detection rate of the 14-core scheme was compared to the one of the other biopsy schemes obtained through the exclusion of pairs of cores. Data were stratified according to the different TRUS estimated prostate volumes. RESULTS: The detection rate of the standard sextant was 35.2%, while those of the 8-core schemes ranged from 37.1 to 38.8%. The 10-core schemes yielded detection rates of 39.6-40.8% and the protocol with 12 biopsies in the peripheral zone diagnosed prostate cancer in 42.1% of the patients. In patients with <30 cc prostate volume, the detection rate of the 14-core scheme was 43.8% and resulted statistically overlapping to the 8-peripheral cores protocol. In patients with 30.1-50 cc prostate volume a 12-peripheral core biopsy reproduced the results of the 14-core sampling. In prostates larger than 50 cc, an even more extensive procedure was mandatory, considering the low detection rate of the 14-core scheme (24.2%). CONCLUSION: Transperineal prostate biopsy is a safe procedure with a very low complication rate and high cancer detection rate. Prostate volume is the most relevant variable in the planning of the optimal number of cores in the extensive first biopsy set. A protocol with more than 8 peripheral cores) is recommended only in patients with prostate volume larger than 30 cc.