Comparative expression of immunohistochemical biomarkers in cribriform and pattern 4 non-cribriform prostatic adenocarcinoma.

The morphology of Gleason 4 prostate cancer (PCa) can be subdivided into cribriform and non-cribriform patterns. A large body of evidence has shown that pattern 4 cribriform PCa (especially non-glomeruloid type) is associated with adverse pathologic features and clinical outcomes compared with non-cribriform pattern 4 PCa. The underlying mechanisms for the aggressiveness of cribriform PCa are not fully understood. The aim of this study is to compare the immunohistochemical expression of various biomarkers and to determine the potential proteins that may account for their biologic and clinical differences. A total of 14 biomarkers were studied. The number of non-glomeruloid cribriform PCa cases studied for each biomarker ranged from 18 to 74 and the number of non-cribriform pattern 4 PCa studied for each biomarker ranged from 29 to 112. We demonstrated that, compared with non-cribriform Gleason pattern 4 PCa, EGFR was significantly upregulated and standard CD44 (CD44s) was significantly downregulated in cribriform PCa; no significant differences were found in the expression of AR, NKX3.1, ERG, EZH2, p53, Rb, C-Myc, BCL2, p16, CyclinD1, Her2/Neu, and Synaptophysin between these two groups of pattern 4 PCa. The study also showed, compared to non-cribriform PCa, cribriform PCa presented with significantly higher serum PSA and more advanced tumor stage. The significant overexpression of EGFR and downregulation of CD44s in non-glomeruloid cribriform PCa may, at least, partly explain the unfavorable pathology and clinical results for this growth pattern. Given that EGFR targeted inhibitors are now available, the findings may also have significant therapeutic implications.

Expression of GATA-3 in Testicular and Gynecologic Mesothelial Neoplastic and Non-neoplastic Tissues.

GATA-3 expression in testicular/gynecologic mesothelial neoplasms and benign mesothelia have not been completely investigated. We graded GATA-3, calretinin, and WT1 staining in 20 adenomatoid tumors [9/20 (para)testicular and 11/20 tubal/uterine] and 38 normal mesothelia (20/38 tunica vaginalis and 18/38 fallopian tubes) as either 0 (≤5%), +1 (>5% and <25%), +2 (≥25% and ≤50%), and +3 (>50%). Adenomatoid tumor GATA-3 staining: 2 urologic cases were positive (2/9, +3 and +1), no gynecologic cases were positive (0/11), and all were positive for WT1/calretinin (20/20,+2 to +3). The normal tunica vaginalis mesothelia: 3 of 20 were GATA-3 positive (+2) while 20 of 20 were WT1/calretinin (+2 to +3) positive. The gynecologic cases with walthard nests: are positive for GATA-3 (18/18,+3), WT1 (11/18, +2 to +3), and calretinin (1/18,+2). The nonmetaplastic gynecologic mesothelia were GATA-3 negative (18/18) and WT1/calretinin postive (18/18,+2 to +3). All 18 epididymi were GATA-3 positive (+3) and negative for WT1/calretinin. All 11 efferent ductules examined were negative for GATA-3, WT1/calretinin (0/11). Although GATA-3 rarely stains adenomatoid tumors, gynecologic walthard nests are consistently positive with GATA-3 staining but lose mesothelial markers reflecting a metaplastic change. Excluding the walthard nests, GATA-3 is rarely positive in normal urologic and gynecologic mesothelia. GATA-3 is uniformally positive in epididymi and negative in efferent ductules, which may be due to their embryological evolvement. Awareness of the GATA-3 staining patterns in the genitourinary and gynecologic mesothelial tissues and their respective neoplasms is important to prevent misdiagnosis and possible unnecessary interventions.

ZBTB16: a novel sensitive and specific biomarker for yolk sac tumor.

Although the function of zinc finger and BTB domain containing 16 (ZBTB16) in spermatogenesis is well documented, expression of ZBTB16 in germ cell tumors has not yet been studied. The aim of this study was to investigate the immunohistochemical expression and diagnostic utility of ZBTB16 in germ cell tumors. A total of 67 adult germ cell tumors were studied (62 testicular germ cell tumors, 2 ovarian yolk sac tumors, 1 mediastinal yolk sac tumor, and 2 retroperitoneal metastatic yolk sac tumors). The 62 testicular primary germ cell tumors are as follows: 34 pure germ cell tumors (20 seminomas, 8 embryonal carcinomas, 2 teratomas, 1 choriocarcinoma, 1 carcinoid, and 2 spermatocytic tumors) and 28 mixed germ cell tumors (composed of 13 embryonal carcinomas, 15 yolk sac tumors, 15 teratomas, 7 seminomas, and 3 choriocarcinomas in various combinations). Thirty-five cases contained germ cell neoplasia in situ. Yolk sac tumor was consistently reactive for ZBTB16. Among the 15 testicular yolk sac tumors in mixed germ cell tumors, all displayed moderate to diffuse ZBTB16 staining. ZBTB16 reactivity was present regardless of the histologic patterns of yolk sac tumor and ZBTB16 was able to pick up small foci of yolk sac tumor intermixed/embedded in other germ cell tumor subtype elements. Diffuse ZBTB16 immunoreactivity was also observed in 2/2 metastatic yolk sac tumors, 1/1 mediastinal yolk sac tumor, 2/2 ovarian yolk sac tumors, 2/2 spermatocytic tumors, 1/1 carcinoid, and the spermatogonial cells. All the other non-yolk sac germ cell tumors were nonreactive, including seminoma (n=27), embryonal carcinoma (n=21), teratoma (n=17), choriocarcinoma (n=4), and germ cell neoplasia in situ (n=35). The sensitivity and specificity of ZBTB16 in detecting yolk sac tumor among the germ cell tumors was 100% (20/20) and 96% (66/69), respectively. In conclusion, ZBTB16 is a highly sensitive and specific marker for yolk sac tumor.

Hemoglobin-Albumin-Lymphocyte-Platelet (HALP) Score as a Predictive Value of Incidental Prostate Cancer for Patients Going for Transurethral Resection of the Prostate (TURP): A Single-Center Study.

Aims Prostate cancer (PC) is a significant health concern worldwide, and early detection is crucial for effective treatment. This study aimed to investigate the role of the hemoglobin-albumin-lymphocyte-platelet (HALP) score in detecting prostate cancer in patients undergoing transurethral resection of the prostate (TURP). Additionally, a comprehensive analysis was performed to explore clinical parameters associated with incidentally diagnosed prostate cancer post TURP. Methods A total of 131 patients with symptomatic bladder outlet obstruction who underwent TURP were included in the study. The patients were divided into two groups: those with benign prostatic hyperplasia (BPH) and those with incidental prostate cancer (IPC). The IPC group consisted of patients with both low-grade and high-grade IPC determined by the Gleason score. Demographic data, including age, race, medical history, body mass index, smoking and alcohol status, and family history of prostate cancer, were evaluated. The postoperative measurement of specimen weight and prostate-specific antigen (PSA) levels were also analyzed. Result Results revealed that approximately 50% of the patients had BPH, while the remaining 50% had IPC. Patients with IPC, particularly high-grade IPC, had significantly higher PSA levels and lower resected specimen weight compared to those with BPH. The HALP score, which incorporates hemoglobin (Hb), albumin, lymphocyte, and platelet levels, showed promise as a discriminatory tool for distinguishing between BPH and IPC, as well as between high-grade IPC and BPH/low-grade IPC. Logistic regression analysis identified increased PSA levels (p=0.02), decreased HALP score (p≤0.001), and smaller specimen weight (p=0.007) as independent predictive factors for IPC after TURP. Notably, the HALP score was the only significant independent predictive factor associated with high-grade IPC (p=0.004). Conclusion These findings contribute to the understanding of risk factors and diagnostic tools for incidentally detected prostate cancer in patients with bladder outlet obstruction undergoing TURP. The HALP score, along with PSA levels and specimen weight, can aid in the early detection and management of prostate cancer. Further research is warranted to validate these findings and explore the clinical utility of the HALP score in predicting prostate cancer outcomes.

KLF6 loss of function in human prostate cancer progression is implicated in resistance to androgen deprivation.

Inactivation of the transcription factor/tumor suppressor Krüppel-like factor 6 (KLF6) has been described in prostate cancer (PC). This study investigated the prevalence and significance of KLF6 exon 2 mutations and splice variants (SVs) in different stages of human PC progression. By using laser-capture microdissection and recombinant clone isolation of DNA sequences to enhance sensitivity, base changes were found in 20 (24.7%) of 81 PC tissues versus 1 (4%) of 25 normal prostate tissues (P = 0.02). Of 26 base changes, 54% produced nonsynonymous mutations. Only three mutations had driver characteristics (PCs, 4%; NPs, 0%). By using microdissection of fresh-frozen tissues and recombinant isolation of RNA sequences, SVs were found in 39 (75%) of 52 PCs and in 10 (45%) of 22 NPs (P = 0.01). Sixteen different SVs, including 13 unique SVs, were identified that used cryptic splicing sites and encoded nonfunctional KLF6 proteins. PCs that had survived hormone (androgen)-deprivation therapy (n = 21) had a significantly higher (P < 0.05) incidence, number, and expression level of nonfunctional SVs than either NPs (n = 22) or hormone-naïve PCs (n = 25). Forced expression of nonfunctional SVs conferred a survival advantage of androgen-dependent LNCaP cells under castration-simulated culture conditions. Together, these data suggest that decreased availability of functional KLF6 contributes to clinical PC progression. This decrease arises infrequently by somatic mutation and more commonly by the acquisition of SVs that provide a survival advantage under castrate conditions, enabling resistance to hormone therapy.

Locally Invasive Papillary Intralymphatic Angioendothelioma Arising Within a Lymphatic/Venous Malformation.

BACKGROUND Papillary intralymphatic angioendothelioma (PILA) is a rare vascular tumor affecting children and young adults, with less than 50 cases reported in the literature. This tumor typically presents in the extremities, exhibits borderline behavior, and has a prominent lymphatic phenotype. Originally thought to be malignant, PILA was later recognized for its borderline behavior and lymphatic features, leading to its current classification as a "rarely metastasizing lymphatic vascular neoplasm". CASE REPORT We present the case of a 10-year-old girl with a 6-year history of a right facial venous malformation, which was ultimately diagnosed as PILA in the background of lymphatic/venous malformation (LVM). After undergoing surgical excision of a right facial soft-tissue tumor, histopathological examination revealed scattered lymphatics and thin-walled vascular channels with blood in skeletal muscle and fibroadipose tissue. Intraluminal papillary proliferation of vascular spaces lined by cytologically bland spindle cells was observed, along with Kaposiform morphology and small-vessel proliferation. Immunohistochemical staining confirmed endothelial cell markers (D2-40, ERG, CD34, and CD31) and numerous CD3(+) lymphocytes in the lumen, surrounded by CD3(+) T lymphocytes and CD20(+) B lymphocytes in the surrounding stroma. The tumor lacked pleomorphism, significant mitotic activity, and necrosis. CONCLUSIONS PILA presents a diagnostic challenge and should be considered in the differential diagnosis of cutaneous vascular neoplasms. Long-term follow-up is crucial due to its borderline behavior and potential for local invasiveness and metastasis. Accurate diagnosis, aided by characteristic histological and immunohistochemical features, is essential for appropriate management of this rare vascular tumor.

Urothelial metaplasia of the seminal vesicles: a report of 2 cases.

Although urothelial metaplasia has been reported in the fallopian tube, urothelium in the seminal vesicle has been rarely reported. We report 2 cases of urothelial epithelium in seminal vesicles from radical prostatectomy specimens. One case involved a 63-year-old patient with pT2c prostatic adenocarcinoma (Gleason pattern 3+4; total score, 7). The other case involved a 60-year-old patient with pT2c prostatic adenocarcinoma (Gleason pattern 4+3; total score, 7; with focal Gleason pattern 5). Representative sections of the left seminal vesicles from both patients demonstrated a portion of urothelial epithelium consisting of 3 to 8 cell layers, which included superficial (umbrella), intermediate, and basal cells. An abrupt transition from the normal single layer of cuboidal cells of seminal vesicle to multilayered urothelium was identified in 1 case, and circumferential urothelium was identified in the other case. No urothelial metaplasia was seen in the prostatic tissue. The histogenesis of urothelial metaplasia in the seminal vesicle is unclear, but it possibly is a reaction to mechanical irritation, inflammation, or infection, as has been proposed for urothelial metaplasia in the fallopian tube and squamous metaplasia of the pelvic peritoneum. Nevertheless, a rare congenital malformation cannot be ruled out as an etiology. Clinical follow-up of patients with urothelial cell metaplasia of the fimbriae suggests that it bears no biologic significance, yielding no instances of carcinoma. However, whether there will be an impact on fertility awaits further study.

Papillary Renal Cell Carcinomas Demonstrating Micropapillary Features: An Investigation Into the Diagnostic and Prognostic Implications.

AIMS: Papillary renal cell carcinoma (PRCC) with micropapillary carcinoma (MC) has been rarely described. We conducted a retrospective descriptive evaluation of the association of MC with PRCC and the possible prognostic implications. METHODS: A database search was made at the University of Southern California (USC) and Lenox Hill Hospital (LHH; New York City) in June 2016-June 2019 of PRCC cases with MC. Diagnosis of MC was made using routine histology, based on the presence of small clusters of cells without a vascular core. Features evaluated included: percent of MC, gross appearance, PRCC typing, nuclear grade, lymphovascular invasion, and lymph node metastasis. RESULTS: 848 RCC cases (690 from USC and 157 from LHH); 70 cases PRCC (54 from USC, 16 from LHH) of these cases, 13 had an MC, 12 were from radical nephrectomy, and 12 cases were male. Mean age was 68.3 years; seven were located in the right kidney. Average tumor size was 8.6 cm. MC ranged from 10% to 80% (average 37.5%), nine cases were PRCC type 2 and four type 1. Nuclear grade: three cases (grade 2), nine cases (grade 3), and one case (grade 4); 11 out of 13 tumors presented with extrarenal extension; nine cases that had lymph nodes submitted had metastatic carcinoma. CONCLUSIONS: The presence of a micropapillary component in PRCC was found to be 18.5%, and it was predominantly associated with high pathologic stage and lymph node metastases. The clinical course of these tumors seems similar to MC in other tissues/organ systems. We advocate reporting this pattern when identified.

Factors associated with late local failure and its influence on survival in men undergoing prostate brachytherapy.

BACKGROUND AND PURPOSE: To determine the factors associated with a positive post-treatment prostate biopsy (PB) and the effects of local failure on biochemical control and cause-specific survival (CSS) in men receiving prostate brachytherapy. METHODS AND MATERIALS: Of 545 men with post-implant PB, 484 were routine (median 24 months) while 61 (median 55 months) were for cause. 114 had a repeat PB for rising PSA. Initial mean PSA was 10.5 ng/ml (±13.9) while 244 (44.8%), 202 (37.1%) and 99 (18.2%) had low, intermediate or high-risk disease. Treatments were implant only in 287 (52.7%), and implant with androgen deprivation therapy (ADT) ± external beam in 258. Radiation doses were converted to the biologically equivalent dose (BED). Final biopsy results were the last biopsy performed on that patient. Associations for the first and final biopsies with PSA, clinical stage (CS), Gleason grade group, time on hormone therapy (ADT) and BED were determined by ANOVA, chi-square and binary linear regression. Freedom from Phoenix failure (FFPF) and cause-specific survival were estimated by Kaplan Meier method and Cox proportions hazards. RESULTS: After a median of 11.4 years the first and final biopsy were positive in 10.8% and 8.8%, respectively. Significant linear regression associations with first positive PB were ADT (p = 0.005), CS (p = 0.044) and BED (p = 0.030) while only BED (p < 0.001) was significant for the final PB. Positive biopsy occurred in 21/112 (18.8%), 16/230 (7.0%) and 3/182 (1.6%) for BED ≤150, >150-200 and >200 Gy (p < 0.001), and in 29/261 (11.1%) for BED (median) ≤185 Gy vs. 5/263 (1.9%) for > 185 Gy (OR 4.2, p < 0.001). 15-year FFPF was 75.6 vs. 17.5% and cause-specific survival was 94.2 vs. 75.5% for negative vs. positive biopsy. CONCLUSIONS: Higher radiation doses are associated with 1.9% late local failure following prostate brachytherapy. A negative post-implant PB is associated with superior FFPF and decreased prostate cancer mortality.

'Mohs surgery of the prostate': the utility of in situ frozen section analysis during robotic prostatectomy.

OBJECTIVE • To evaluate a novel technique to lower positive surgical margin rates while preserving as much of the neurovascular bundles as possible during nerve-sparing robotic prostatectomy. MATERIALS AND METHODS • In situ intraoperative frozen section (IFS) was performed during robotic-assisted laparoscopic prostatectomy (RALP) when there was macroscopic concern for a positive margin or residual prostate tissue. • When IFS was positive, additional sections were taken from the same area until the IFS was negative, similar to the procedure of Mohs micrographic surgery. • Positive surgical margin and biochemical recurrence rates were compared between the patients who underwent IFS and those who did not. RESULTS • Of 970 patients consecutively undergoing RALP at a single institution, IFS was performed on 177 (18%). • Eleven patients (6%) had IFS positive for carcinoma, whereas another 25 (14%) had benign prostatic tissue in the IFS specimen. • IFS and non-IFS patients had similar pathological and nerve-sparing characteristics. • The IFS group had significantly lower rates of positive surgical margins, 7% vs 18% (P = 0.001) but similar rates of biochemical recurrence (5%) at a median follow-up of 11 months. CONCLUSIONS • In situ IFS is an effective way of reducing positive margins during RALP. • Twenty percent of patients who underwent IFS, representing 4% of the overall RALP population, had either malignant or benign prostate tissue removed from their prostatic fossa. • Although a reduction of biochemical recurrence was not demonstrated, the follow-up is short and a difference may become apparent as the data mature.

Renal pelvic urothelial carcinoma with divergent morphology.

Compared with that of urinary bladder, urothelial carcinoma of renal pelvis is infrequent and its morphologic features and presentations have seldom been described. Fifty-nine renal pelvic urothelial carcinomas were evaluated in this study. Seventy-eight percent of these were high-grade tumors, of which 39% contained variable amount of divergent morphology. Forty-four percent of the high-grade urothelial carcinomas presented with an advanced tumor stage. Seventy-eight percent of urothelial carcinomas with divergent morphology displayed a tumor stage of pT2 and above, compared with 21% of classical urothelial carcinomas, which presented at stage pT2 and above. In summary, high-grade and unusual morphology as well as advanced tumor stage were the frequent findings in pelvicalyceal urothelial carcinomas. In addition, divergent morphology was correlated with advanced tumor stage. The clinicopathologic features of pelvicalyceal urothelial carcinomas with unusual divergent morphology were particularly emphasized in this study.

Clinicopathologic and Immunohistochemical Study of Combined Small Cell Carcinoma and Urothelial Carcinoma Molecular Subtype.

Muscle invasive bladder cancer, an aggressive disease with heterogeneous molecular profiles, has recently been subclassified into three major molecular subtypes -basal, luminal and "p53-like" urothelial carcinomas (UCas), which bear prognostic and therapeutic implication. Similar to breast cancer, basal and luminal subtype UCas are designated by basal (CK5/14) and luminal (CK20) markers. The "p53-like" subtype presents with wild-type p53 gene with upregulated p53 pathways and is implicated in chemoresistance. Urinary bladder is one of the most common primary sites of extrapulmonary small cell carcinoma (SmCC). Bladder SmCC frequently coexists with UCa; however, the relation of SmCC with specific UCa molecular subtypes has not been studied. The aim of this study is to investigate the clinicopathology and immunophenotypes of the combined SmCC and UCa molecular subtypes. A total of 22 combined SmCC and UCa cases were studied for the clinicopathology and immunohistochemical (IHC) profiles by luminal and basal cell markers as well as Her2/Neu and p53. Our results demonstrated that all the urinary bladder SmCCs were associated with high grade UCas. They were more commonly seen in older male patients with a smoking history and had a poor prognosis. Based on the reported molecular subtyping, the UCas could be immunohistochemically subclassified into luminal, basal, dual and null types, which showed different clinicopathologic and IHC features. Compared to non-SmCC associated UCa, the subtypes of UCa in the combined SmCCs and UCas were characterized by: 1) Although overall luminal type was still relatively more common in men, basal marker-expressing subtypes were significantly increased in incidence and were more common in women. 2) Her2/Neu overexpression was more commonly observed in luminal than basal cell marker-expressing UCas. 3) IHC overexpression of p53 was common in all the subtypes, with UCas and SmCCs sharing the same p53 expression pattern. Although limited by relatively a small number of cases, the results of this study will enhance our understanding of the combined SmCC and UCa entity and potentially lead to a future therapeutic management.

Intratubular Teratoma: A Rare Form of Testicular Germ Cell Neoplasia.

Germ cell neoplasia in situ is the initial manifestation for invasive germ cell tumor. Further progression will result in intratubular germ cell tumor with the majority being intratubular seminoma or intratubular embryonal carcinoma. Intratubular teratoma in the testis is exceptionally rare with no well-documented cases to our knowledge. In this article, we report a case of an intratubular teratoma adjacent to mixed germ cell tumor in the testis. The patient is a 34-year-old male who presented with a palpable right testicular mass and underwent right radical orchiectomy. Gross examination of the testis revealed 2.0-cm tan, well-circumscribed, firm, and nodular mass at the inferior pole. Microscopic examination revealed a mixed germ cell tumor, predominantly seminoma (95%) with embryonal carcinoma (4%) and teratoma (1%). There is also germ cell neoplasia in situ, intratubular seminoma, and intratubular teratoma at the periphery of the tumor. Tubules with intratubular teratoma were filled by neoplastic squamous cells with a single layer of germ cell neoplasia in situ at the periphery. Adjacent to the intratubular teratoma was seminoma, embryonal carcinoma, and invasive teratoma. Immunohistochemical stains showed the neoplastic squamous cells in the tubule to be positive for p40 and negative for OCT34 and D2-40. The single layer of germ cell neoplasia in situ at the periphery of the intratubular teratoma was negative for p40 and positive for OCT34 and D2-40. Although teratoma is a common component in an adult germ cell tumor, an intratubular manifestation is exceptional. The present case illustrates this rare finding.

Distant and local recurrence in patients with biochemical failure after prostate brachytherapy.

PURPOSE: To analyze the patterns of failure after the brachytherapy management of localized prostate cancer. METHODS AND MATERIALS: From 1990 to 2008, 2869 patients underwent prostate brachytherapy and 213 experienced a prostate-specific antigen (PSA) failure by the Phoenix definition. Of these 213 patients, 33.5% were low, 18.5% intermediate, and 58% high risk. RESULTS: Of the 119 patients biopsied, 36 (30%) had a least one positive posttreatment biopsy. In univariate and multivariate analyses, PSA doubling time was the most predictive of a positive biopsy. Patients with doubling times < or =3, >3-6, > or =6-10, and >10 months had positive biopsy rates of 9%, 18%, 36%, and 42%, respectively (p=0.01). The actuarial rate of remaining free from distant metastases at 10 years was 73%. Patients with PSA doubling times of < or =3, >3-6, >6-10, and >10 months had freedom from distant metastases rates of 0%, 74%, 78%, and 94.5% at 10 years, respectively (p<0.0001). In multivariate analysis, PSA doubling time and time to PSA failure were the most significant predictors of developing distant metastases. CONCLUSIONS: About one third of patients harbor a component of local failure and one fourth demonstrate clinical metastases. PSA doubling time can be used to help predict the source of a rising PSA.

Renal benign epithelial nodal inclusions.

There are 3 case series reports describing benign epithelial inclusions in nodal sinuses of perinephric lymph nodes of pediatric patients. The majority of these inclusions were observed in perinephric lymph nodes removed during nephrectomies from pediatric patients with Wilms' tumors. We report 2 cases of benign renal tubular epithelial inclusions located in the perinephric hilar lymph nodes. One of our cases is, to our knowledge, the first case of benign renal epithelial inclusions reported in an adult patient.

Focal Signet Ring Cell High-Grade Prostatic Intraepithelial Neoplasia on Needle Biopsy.

Signet ring cell prostatic intraepithelial neoplasia is a rare speculated variant of high-grade prostatic intraepithelial neoplasia (HGPIN). Here, we present a free-standing and isolated signet ring cell HGPIN that was not associated with invasive carcinoma on needle biopsy and demonstrated the existence of this type of HGPIN variant. The differentiation between HGPIN and intraductal carcinoma of prostate is also discussed.

Sertoliform Cystadenoma of the Rete Testis: Report of a Case and Review of the Literature.

Sertoliform cystadenoma is a rare benign tumor of the rete testis with 8 previously reported cases and an additional 14 cases reported in an abstract form. It usually presents with a unilateral scrotal mass, clinically and radiologically indistinguishable from malignant testicular tumors. We report a 39-year-old man who presented with a right testicular mass. The patient underwent radical inguinal orchiectomy. Grossly, no masses were appreciated. After histologic examination with subsequent immunohistochemical staining, a sertoliform cystadenoma of the rete testis was diagnosed.

Do Nonseminomatous Germ Cell Tumors of the Testis With Lymphovascular Invasion of the Spermatic Cord Merit Staging as pT3?

The staging of testicular nonseminomatous germ cell tumors (NSGCTs) with lymphovascular invasion (LVI) of the spermatic cord in the absence of cord parenchymal involvement remains controversial. Our previous study showed that tumors with spermatic cord LVI present at a higher clinical stage than tumors with LVI confined to the testis (pT2). We compared NSGCTs with LVI of the spermatic cord without direct involvement of the spermatic cord soft tissues to pT3 tumors to help clarify the appropriate staging of this histologic finding. A retrospective, multi-institutional review was performed to identify cases of NSGCTs with LVI in the spermatic cord without soft tissue invasion of the cord. The clinical-pathologic findings were compared with NSGCTs with spermatic cord soft tissue invasion (pT3). We identified 38 pT2 NSGCTs with LVI in the spermatic cord without soft tissue invasion of the cord and 89 pT3 tumors. There were no significant differences in patient age, tumor size, or clinical stage at presentation between the 2 groups. There were no significant differences in dominant histologic subtype, rete testis invasion, hilar soft tissue invasion, or margin status. There were no significant differences in disease recurrence/progression (P=0.63), recurrence/progression after chemotherapy (P=0.35), or death (P=0.51) between patients with only spermatic cord LVI versus patients with cord soft tissue invasion. In patients with pT2 NSGCTs according to the current staging, LVI in the spermatic cord without cord soft tissue invasion is comparable with pT3 tumors in terms of clinical stage at presentation as well as disease recurrence and survival.

Diagnosis and management of local recurrence after low-dose-rate brachytherapy.

OBJECTIVES: To describe the diagnosis of local failure after prostate brachytherapy (BT) and treatment options when recurrence is present. METHODS AND MATERIALS: Review of literature for local recurrence after prostate BT and salvage therapy was performed. A total of 6 patients with prostate-specific antigen increase were identified as local failures by transperineal mapping biopsy (TPMB) and treated with targeted focused therapy using cryoablation. RESULTS: Local recurrence after prostate BT occurs in 2-20% and is dose dependent. The biologic effective dose greater than 200 Gy(2) is associated with a less than 2% recurrence rate. Confirmatory biopsy should include both the prostate and seminal vesicles, as prostate cancer can be found in 20% of the latter. The pathologist should be experienced in evaluating post-irradiation tissue because of the difficulty in distinguishing benign irradiated prostate from residual or recurrent tumor. Whole gland salvage, whether by prostatectomy or cryoablation, is associated with high complication rates. Focal therapy has fewer complications but accurate targeting remains a concern. Newer diagnostic and targeting modalities such as multiparametric MRI and TPMB offer improved opportunity to increase lesion identification and ablation. A TPMB approach, which incorporates new biopsy needle design and interactive targeting software, may offer the best avenue to true focused therapy. CONCLUSION: Local recurrences after prostate BT are uncommon because of high delivered radiation dose. When present, improved lesion identification and targeting may be associated with better cancer control and lower morbidity.

Loss of PLZF expression in prostate cancer by immunohistochemistry correlates with tumor aggressiveness and metastasis.

PLZF is a transcription repressor, which plays a critical role in development, spermatogenesis and oncogenesis. Down-regulation of PLZF has been found in various tumor cell lines. There has been virtually no tissue study on the expression of PLZF in prostate cancer (PCa). PCa is a heterogeneous disease, most of which are indolent and non-lethal. Currently there are no biomarkers that distinguish indolent from aggressive PCa; therefore there is an urgent need for such markers to provide clinical decision support. This study aimed to investigate the expression of PLZF by immunohistochemistry in different grade as well as metastatic PCa and to correlate the alteration of PLZF expression with PCa aggressiveness. We studied a total of 83 primary PCa from biopsies, 43 metastatic PCa and 8 paired primary and metastatic PCa from radical prostatectomies with lymph node dissection. Our results demonstrated that PLZF was strongly expressed in almost all (~100%) benign luminal cells (n=77) and low grade (Gleason pattern 3) PCa (n=70) and weak or absent (100%) in basal cells (n=70). Decreased or lost expression of PLZF was evidenced in 26% of high-grade (Gleason 4 and 5) primary PCa (n=70) and 84% metastatic PCa (n=43). The primary high grade PCa in the prostatectomies shared similar PLZF loss/decrease and histomorphology to that of paired parallel lymph node metastases. These data demonstrated that down-regulation of PLZF is an important molecular process for tumor progression and loss of PLZF expression detected by routine immunohistochemistry is a promising and valuable biomarker for PCa aggressiveness and metastasis in the personalized care of PCa.