Adenoid cystic carcinoma metastatic to the kidney: a series of 10 patients emphasizing unilateral presentation and long time interval from primary diagnosis.

Adenoid cystic carcinoma (AdCC) metastasis to kidney is rare. We identified 10 patients with metastatic AdCC in multi-institutional collaboration. Core needle biopsy was the most common specimen (n = 6). Patients were predominately female (n = 7) with a median age of 48 years (35-62 years). The most common primary location of the AdCC was head and neck (n = 6, among them parotid gland = 4), followed by lung (n = 2), breast (n = 1), and vulva (n = 1). Median lapse between primary AdCC and renal metastasis was almost 13 years (154 months, range 1-336 months). Moreover, all but one patient had unilateral kidney metastasis. The majority of metastatic AdCC within the kidney demonstrated mixed growth patterns, frequently cribriform, and tubular morphology. Follow-up available for 8 patients showed 6 alive with disease and 2 died of disease (the longest survival was 4 years past the diagnosis of renal metastasis). A systematic literature review including 29 patients revealed that kidney metastasis by AdCC is usually a late event, is typically unilateral, and is usually composed of one to three foci, and thus has clinical features which mimic a primary renal tumor.

What's new in genitourinary pathology 2023: WHO 5th edition updates for urinary tract, prostate, testis, and penis.

The 5th edition WHO Classification of Urinary and Male Genital Tumours (2022) introduced many significant changes relevant to urologic daily practice, mainly to renal tumors which was covered in the What's New newsletter in September 2022. In this newsletter, we summarize the notable changes to bladder, prostate, testis, and penis based on the 5th edition of the WHO.

The stratification of positive lymph nodes into pN1 and pN2 for upper urinary tract carcinoma is not prognostically significant.

The 3rd-7th edition of the American Joint Committee on Cancer had 3 categories for positive lymph nodes (pN1-3) in upper urinary tract carcinomas. The 8th edition removed pN3, defining pN1 as one lymph node with a tumor deposit ≤2 cm and pN2 as a node with a tumor deposit >2 cm or metastases in multiple nodes. The aim of this study was to assess if the current pN categories impact survival in renal pelvic and ureteral carcinomas. Nephroureterectomies performed at our institution for primary upper urinary tract carcinomas between 2010 and 2019 were reviewed. Lymphadenectomy was performed in 73.3% of cases (151/206, median = 9 nodes). Eighty-one (53.6%) patients were deceased at the last review (pN0, 53 [44.5%]; pN1-2, 28 [87.5%]). There was no difference in overall or recurrence-free survival between pN1 and pN2 with 5-year overall survival (95% confidence interval) of pN0, 60.7% (52.0-70.8%); pN1, 15.4% (4.3-35.2%); and pN2, 21.1% (8.8-40.3%). The metastatic deposit size threshold of 2 cm, the number of positive lymph nodes, as well as extranodal extension did not correlate with overall or recurrence-free survival. As such, pN1 and pN2 were grouped together with a 5-year overall survival of 18.8% (9.12-28.6%). The current stratification of upper urinary tract carcinomas into pN1 and pN2 does not provide prognostic information, and both yield a stage IV classification, regardless of pT or pM category. Therefore, we recommend further simplification of pN classification into one category for regional lymph node metastasis, irrespective of the lymph node deposit size or number of positive lymph nodes.

Renal Pelvic Urothelial Carcinoma With Invasion Into Renal Medulla Can Be Redefined as pT2 to Improve Correlation With Survival.

According to the American Joint Cancer Committee, pT3 renal pelvic carcinoma is defined as tumor invading the renal parenchyma and/or peripelvic fat and is the largest pT category, with notable survival heterogeneity. Anatomical landmarks within the renal pelvis can be difficult to discern. Using glomeruli as a boundary to differentiate renal medulla invasion from renal cortex invasion, this study aimed to compare patient survival of pT3 renal pelvic urothelial carcinoma on the basis of the extent of renal parenchyma invasion and, thereafter, determine whether redefining pT2 and pT3 improves pT correlation with survival. Cases with primary renal pelvic urothelial carcinoma were identified through a review of pathology reports from nephroureterectomies completed at our institution from 2010 to 2019 (n = 145). Tumors were stratified by pT, pN, lymphovascular invasion, and invasion of the renal medulla versus invasion of the renal cortex and/or peripelvic fat. Overall survival between groups was compared using Kaplan-Meier survival models and Cox regression multivariate analysis. pT2 and pT3 tumors had similar 5-year overall survival, with multivariate analysis demonstrating an overlap between hazard ratios (HRs) for pT2 (HR, 2.20; 95% CI, 0.70-6.95) and pT3 (HR, 3.15; 95% CI, 1.63-6.09). pT3 tumors with peripelvic fat and/or renal cortex invasion had a 3.25-fold worse prognosis than pT3 tumors with renal medulla invasion alone. Furthermore, pT2 and pT3 tumors with only renal medulla invasion had similar overall survival, whereas pT3 tumors with peripelvic fat and/or renal cortex invasion had a worse prognosis (P = .00036). Reclassifying pT3 tumors with only renal medulla invasion as pT2 yielded greater separation between survival curves and HR. Thus, we recommend redefining pT2 renal pelvic carcinoma to include renal medulla invasion and restricting pT3 to peripelvic fat and/or renal cortex invasion to improve the prognostic accuracy of pT classification.

Implementation of a required 3rd-year medical student surgical pathology clinical experience.

Few medical schools have required experience â€‹in surgical pathology during the clinical years. After introducing a pilot and preliminary surgical pathology clinical experience into the curriculum, we initiated a required 3rd-year medical student surgical pathology clinical experience that consisted of a one hour introductory lecture; one hour gross room, histology, and immunohistochemistry laboratory introduction; and one hour of one-on-one case sign-out preceptorship with a subspecialty surgical pathologist within the surgery and obstetrics/gynecology block. Concepts that were covered included specimen processing, intraoperative frozen section consultation, completing specimen requisitions, interpreting synoptic reports, and pTNM staging. Students evaluated the surgical pathologist from 1 to 5 (1 "poor/unhelpful," 2 "marginal," 3 "neutral," 4 "good," 5 "excellent/useful"). Ten multiple-choice questions (included as part of a perioperative services exam) and attendance were incorporated into students' perioperative services rotation grade. From 2014 to 2018, 757 students participated in the required 3rd-year surgical pathology clinical experience. Thirty academic subspecialty pathologists acted as preceptors with an average of nine sessions per preceptor per year. Evaluation data from 316 students from 2015 to 2018 showed a mean preceptor rating of 4.8/5 (range 4.0-5.0). Students scored an average of 81% on the surgical pathology portion of the exam (range 21-99% for each question). We successfully implemented a required medical student surgical pathology clinical experience. At the clerkship's conclusion, students demonstrated understanding of key concepts and rated their preceptorship experience highly.

Clinicopathologic features of scrotal leiomyosarcoma: single institutional experience of ten cases.

Scrotal leiomyosarcoma arises from the subcutaneous smooth muscle layer and is an exceptionally rare disease process, with only six patients in the largest reported case series. This rarity creates uncertainties regarding diagnosis, surgical management, and clinical outcomes. Our purpose was to retrospectively describe our institutional experience with scrotal leiomyosarcoma from 2010 to 2022. Slides were reviewed with case inclusion requiring both nuclear atypia and mitotic activity. Ten patients with scrotal leiomyosarcoma were identified. Clinical impression included scrotal cyst in nine cases. The median age at diagnosis was 52 years (range: 29-75 years). The mean tumor size was 1.6 cm (range: 0.4-3.7 cm). Margins were positive in three cases and close in one case, prompting four re-excisions. The mean mitotic rate was 2.3 per 10 high-power field (range: 1-11), with mean Ki67 of 4.6% (range: 1-15%). Nine of the tumors were grade 1, while 1 was grade 2. Four patients had disease-specific follow-up. The remaining six patients have not had disease-specific surveillance. None of the ten patients have shown evidence of recurrence (median follow-up: 75 months, range: 0-116 months). Our series demonstrates that scrotal leiomyosarcoma has a deceptive clinical presentation with a wide age range and small tumor size. With complete surgical resection, scrotal leiomyosarcoma has an excellent prognosis and rigorous follow-up or adjuvant treatment is not likely to be necessary. Cases with unusual clinical or pathologic findings, such as large tumor size or high mitotic rate, may merit more intensive disease-specific surveillance.

Reclassifying pT3 renal pelvic urothelial carcinoma with renal parenchyma invasion to pT2 improves correlation with overall survival.

The American Joint Cancer Committee pT categorization in renal pelvic carcinoma defines pT3 as invasion of renal parenchyma, invasion of peripelvic fat, or both. However, survival heterogeneity within the pT3 category has been demonstrated. This investigation sought to compare survival between pT categories of renal pelvic urothelial carcinoma and identify modifications to improve correlation with survival. Pathology reports from nephroureterectomies performed at our institution from 2010 to 2019 were analyzed to identify primary renal pelvic urothelial carcinoma (n = 146). Tumors were stratified based on pT, pN, and invasion of renal parenchyma vs invasion of peripelvic fat with or without renal parenchyma invasion. Kaplan-Meier survival curves and Cox regression multivariate analysis were used to compare overall survival between groups. Similar survival curves were observed for pT2 and pT3 tumors. Multivariate analysis confirmed overlapping hazard ratios (HRs) for pT2 (HR = 2.64, 95% confidence interval [CI] = 0.69, 10.06) and pT3 (HR = 4.42, 95% CI = 2.08, 9.37). pT3 tumors with peripelvic fat invasion, regardless of renal parenchyma involvement, had a 3.3-fold worse overall survival than pT3 tumors with only renal parenchyma involvement. Additionally, pT3 tumors with only renal parenchyma invasion had similar survival compared to pT2, while pT3 tumors with peripelvic fat invasion had worse overall survival (p = 0.00091). Reclassifying renal parenchyma invasion as pT2 yielded greater survival curve separation and greater difference in HRs. For renal pelvic urothelial carcinoma, modifying the pT3 category to only include tumors with peripelvic fat invasion and expanding the pT2 category to include renal parenchyma invasion may improve pT correlation with overall survival.

Testicular Germ-Cell Tumors with Spermatic Cord Involvement: A Retrospective International Multi-Institutional Experience.

The 8th Edition of the American Joint Committee on Cancer (AJCC) Staging Manual designates discontinuous involvement of spermatic cord soft tissue by testicular germ cell tumors as a metastatic deposit. We conducted a retrospective international multi-institutional study to validate the current recommendations. Thirty-three (72%) nonseminomatous and 13 (28%) seminomatous testicular germ cell tumors were collected from 15 institutions in America, Europe, and Asia. Testicular tumor size ranged from 1.3 to 18.0 cm (mean: 6.1). Cases were classified as discontinuous involvement of spermatic cord soft tissue (n = 26), continuous cord involvement (n = 17), or cord lymphovascular invasion (n = 3). The mean follow-up was 39 months. Clinical stage for discontinuous involvement of spermatic cord soft-tissue patients was I (local disease) in 2/24 (8%), II (regional disease) in 6/24 (25%), and III (distant disease) in 16/24 (67%) cases; 16 (67%) patients presented with distant metastasis. Clinical stage for continuous cord involvement patients was I in 9/17 (53%), II in 4/17 (23%), and III in 4/17 (23%); 4 (23%) patients presented with distant metastasis. Disease progression was seen in 4 patients with discontinuous involvement of spermatic cord soft tissue and 5 with continuous cord-involvement (p = 0.699). When comparing discontinuous and continuous cord involvement, a significant difference was found in cord margin status (p = 0.044), spermatic cord tumor size (p = 0.016), lymph-node involvement (p = 0.037), distant metastasis (p = 0.010), individual clinical stage (p = 0.003), and nonadvanced vs. advanced disease (p = 0.003) at presentation. In multivariate analysis, after adjusting for age, histology, testicular tumor size, percent of embryonal carcinoma, lymphovascular invasion, and cord margin status, discontinuous involvement of spermatic cord soft tissue was significantly associated (p = 0.011) with advanced clinical stage at presentation. Our findings support the designation of metastatic disease for discontinuous involvement of spermatic cord soft tissue, as introduced by the 8th edition of the AJCC staging.

Diagnostic approach in TFE3-rearranged renal cell carcinoma: a multi-institutional international survey.

Transcription factor E3-rearranged renal cell carcinoma (TFE3-RCC) has heterogenous morphologic and immunohistochemical (IHC) features.131 pathologists with genitourinary expertise were invited in an online survey containing 23 questions assessing their experience on TFE3-RCC diagnostic work-up.Fifty (38%) participants completed the survey. 46 of 50 participants reported multiple patterns, most commonly papillary pattern (almost always 9/46, 19.5%; frequently 29/46, 63%). Large epithelioid cells with abundant cytoplasm were the most encountered cytologic feature, with either clear (almost always 10/50, 20%; frequently 34/50, 68%) or eosinophilic (almost always 4/49, 8%; frequently 28/49, 57%) cytology. Strong (3+) or diffuse (>75% of tumour cells) nuclear TFE3 IHC expression was considered diagnostic by 13/46 (28%) and 12/47 (26%) participants, respectively. Main TFE3 IHC issues were the low specificity (16/42, 38%), unreliable staining performance (15/42, 36%) and background staining (12/42, 29%). Most preferred IHC assays other than TFE3, cathepsin K and pancytokeratin were melan A (44/50, 88%), HMB45 (43/50, 86%), carbonic anhydrase IX (41/50, 82%) and CK7 (32/50, 64%). Cut-off for positive TFE3 fluorescent in situ hybridisation (FISH) was preferably 10% (9/50, 18%), although significant variation in cut-off values was present. 23/48 (48%) participants required TFE3 FISH testing to confirm TFE3-RCC regardless of the histomorphologic and IHC assessment. 28/50 (56%) participants would request additional molecular studies other than FISH assay in selected cases, whereas 3/50 participants use additional molecular cases in all cases when TFE3-RCC is in the differential.Optimal diagnostic approach on TFE3-RCC is impacted by IHC and/or FISH assay preferences as well as their conflicting interpretation methods.

NCL Inhibition Exerts Antineoplastic Effects against Prostate Cancer Cells by Modulating Oncogenic MicroRNAs.

Prostate cancer (PCa) is the most frequently diagnosed cancer in men and second most common cause of cancer-related deaths in the United States. Androgen deprivation therapy (ADT) is only temporarily effective for advanced-stage PCa, as the disease inevitably progresses to castration-resistant prostate cancer (CRPC). The protein nucleolin (NCL) is overexpressed in several types of human tumors where it is also mislocalized to the cell surface. We previously reported the identification of a single-chain fragment variable (scFv) immuno-agent that is able to bind NCL on the surface of breast cancer cells and inhibit proliferation both in vitro and in vivo. In the present study, we evaluated whether NCL could be a valid therapeutic target for PCa, utilizing DU145, PC3 (CRPC), and LNCaP (androgen-sensitive) cell lines. First, we interrogated the publicly available databases and noted that higher NCL mRNA levels are associated with higher Gleason Scores as well as with recurrent and metastatic tumors. Then, using our anti-NCL scFv, we demonstrated that NCL is expressed on the surface of all three tested cell lines and that NCL inhibition results in reduced proliferation and migration. We also measured the inhibitory effect of NCL targeting on the biogenesis of oncogenic microRNAs such as miR-21, -221 and -222, which was cell context dependent. Taken together, our data provide evidence that NCL targeting inhibits the key hallmarks of malignancy in PCa cells and may provide a novel therapeutic option for patients with advanced-stage PCa.

Clinicopathologic analysis of renal cell carcinoma containing Intratumoral fat with and without osseous metaplasia.

BACKGROUND: There is minimal information regarding the prevalence of intratumoral adipose in renal cell carcinoma (RCC), and no study has assessed the impact of intratumoral adipose on the preoperative imaging diagnosis. The aim of this study was to investigate the prevalence and histopathologic characteristics of entrapped adipose with or without osseous metaplasia in RCC nephrectomy specimens and to determine if this finding impacted the preoperative imaging interpretation. METHODS: 704 RCC specimens were prospectively evaluated for entrapped adipose and osseous metaplasia (423 partial nephrectomies, 281 total nephrectomies; 327 pT1a, 377 ≥ pT1b; 510 clear cell, 119 papillary, 30 chromophobe, 22 clear cell papillary, 23 other). Imaging reports were obtained, and the presence of intratumoral fat or calcification and the radiologic diagnostic impression were recorded. RESULTS: 3% (n = 21) contained microscopically identified intratumoral adipose, with a similar frequency in the main histologic subtypes (p = 0.76). Mean metaplastic deposit size was 0.4 cm, mean deposit to capsule distance 0.2 cm, and 29% involved the tumor capsule. Histologically identified adipose was infrequently noted via imaging (13%), and only 1 case with histologically identified metaplasia had a radiologic diagnostic differential of angiomyolipoma (1/704, 0.1%). CONCLUSION: While intratumoral adipose and/or osseous metaplasia can be observed within RCC, it is extremely rare for the radiologic diagnostic impression to have been confounded by histologically identified entrapped adipose. Awareness that metaplastic deposits are usually near the tumor capsule and may be minute could help prevent errors in diagnosis or staging.

Does the addition of AMACR to CK20 help to diagnose challenging cases of urothelial carcinoma in situ?

BACKGROUND: Urothelial carcinoma in situ (CIS) in the bladder can be difficult to diagnose due to factors including procedural artifact, minimal tissue sampled, therapy-related changes, and various CIS growth patterns. Prior data has demonstrated an increase in alpha-methylacyl-CoA-racemase (AMACR) in urothelial CIS, but there is no information on its utility for diagnosing difficult cases. The aim of this investigation was to assess the expression of AMACR that was ordered on equivocal bladder cases during clinical practice. METHODS: Transurethral resections of the bladder in which AMACR and CK20 were performed during diagnostic workup were identified and cases with a final diagnosis of CIS (n = 22) or non-neoplastic urothelium (n = 30) were selected. Additionally, cases in which a diagnosis of CIS was rendered without IHC (n = 20) were selected and tested for AMACR expression. RESULTS: Sensitivity of AMACR for CIS diagnosed with IHC during clinical practice was 73% and specificity was 97%, while CK20 was 95% sensitive and 80% specific. Sensitivity of AMACR in CIS diagnosed without IHC was 100%. In all groups, AMACR had inconsistent intensity, compared to CK20 which had consistent, strong intensity. CONCLUSIONS: AMACR was usually positive in urothelial CIS and negative in non-neoplastic urothelium. However, it is important to note that AMACR was less sensitive in difficult cases, while CK20 was more sensitive with more consistent, strong staining compared to AMACR.

Diagnostic terminology used to describe atypia on breast core needle biopsy: correlation with excision and upgrade rates.

BACKGROUND: Subjective qualitative descriptors are sometimes used to describe atypical breast lesions diagnosed on core needle biopsy (CNB) which are limited in extent. In clinical practice, this terminology is used to imply a lower expected risk of upgrade on surgical excision (EXC). It is uncertain how subjective terminology impacts clinical management. METHODS: We conducted a retrospective review of CNB with atypia and compared the EXC and upgrade rates of atypical ductal hyperplasia (ADH) and flat epithelial atypia (FEA) to lesions described as "focal" atypical ductal hyperplasia (FADH), to determine the impact of this diagnostic phrasing on surgical management and risk of malignancy. RESULTS: FADH and ADH were excised at similar rates (82% vs. 78%). FADH lesions showed a similar upgrade rate (13%) compared to non-focal ADH (10%), and both showed a trend towards higher upgrade and EXC rates compared to FEA. ADH, FADH and FEA all had an upgrade risk that warranted EXC. In non-upgraded EXC, for each diagnostic category we observed similar rates of residual atypia in the EXC. CONCLUSIONS: Pathologists should avoid the use of qualitative descriptors when describing ADH on CNB because of the potential of this terminology to influence clinical decision making which is unwarranted.

Impact of the 2018 ASCO/CAP HER2 Guideline Focused Update.

OBJECTIVES: The 2018 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) human epidermal growth factor receptor 2 (HER2) guideline focused update revises the HER2 scoring criteria. We evaluated the impact on HER2 rates in breast carcinoma diagnosed at our center. METHODS: In a retrospective series of breast core biopsies with invasive carcinoma diagnosed between 2014 and 2017 (n = 1,350), HER2 status was classified according to 2013 and 2018 ASCO/CAP guidelines and changes in HER2 status identified. RESULTS: The 2018 guidelines reclassified the HER2 status of 6% of patients. Most changed from HER2 equivocal status (equivocal by immunohistochemistry and fluorescence in situ hybridization under the 2013 guidelines) to HER2-negative status (2018 guidelines). The HER2-positive rate decreased by 0.4%. CONCLUSIONS: The 2018 guidelines decrease the rate of HER2 equivocal and positive breast cancer and reduce repeat HER2 testing on excision specimens. Approximately 0.4% of patients will become newly ineligible for anti-HER2 therapy.

Clinical Utility of Fluorescence In Situ Hybridization (FISH) for Deletion of Chromosome 3p in the Work-up of Renal Masses.

Chromosome 3p deletion is a well-established genetic aberration in clear cell renal cell carcinoma (RCC). We aimed to evaluate the clinical utility of 3p fluorescence in situ hybridization (FISH) on formalin-fixed paraffin-embedded tissue in surgical pathology specimens. 3p:3q <0.8 was established as the cut-off for 3p loss. The 2015 Medicare allowable billing rates were used to estimate the cost. Over 2.5 years (2013 to 2015), 3p FISH was performed on 18 cases per year. Among tested cases, 70% (30/43) were nephrectomies and 30% (14/43) metastases. 3p loss was detected in 44% (19/43) of cases, with a higher rate of loss in radical compared with partial nephrectomies (71% vs. 15%; P=0.003). A definitive RCC subtype was assigned in 65% (28/43) of cases. More partial nephrectomies had a definitive subtype assigned, compared with radical nephrectomies (92% vs. 59%; P=0.04), possibly related to more high-grade, high-stage tumors in submitted radical nephrectomies. Tested nephrectomies were most commonly diagnosed as clear cell (41%) or clear cell papillary RCC (32%). Half of unclassifiable RCCs had 3p loss (53%, 8/15). Annual 3p FISH costs were $3446.64, with 79% of costs from ancillary studies attributable to immunostains. 3p FISH was performed infrequently in nephrectomy specimens and was not cost prohibitive. RCC cases that are unclassifiable by morphology and other ancillary tests, but which have 3p FISH deletion may merit a comment in the pathology report, raising the possibility of clear cell RCC, as the oncologic approach may be altered despite the lack of a definitive RCC subtype.

A combination of GATA3 and SOX10 is useful for the diagnosis of metastatic triple-negative breast cancer.

In metastatic breast cancer (MBC), it can be difficult to establish the origin if the primary tumor is triple negative or if there is a loss of biomarker expression. SOX10 expression has been reported in primary triple-negative breast cancer but is poorly studied in metastatic lesions. In this study, the diagnostic utility of a panel of SOX10, GATA3, and androgen receptor (AR) in MBC negative for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 was evaluated and compared with the expression of these markers in the matched primary breast cancer. In a series of 57 triple-negative MBCs, 82% were positive for GATA3, 58% for SOX10, and 25% for AR. Nearly all MBCs (95%) were positive for either GATA3 or SOX10, with 46% dual positive and 5% of cases negative for both markers. Most GATA3-negative MBC cases were SOX10 positive (70%). AR expression was only seen in GATA3-positive MBC (25%) and was significantly more frequent in SOX10-negative MBC (48%) versus SOX10-positive MBC (9%; P = .001). Concordance for GATA3, SOX10, and AR between the primary and metastasis was 89%, 88%, and 80%, respectively. Although GATA3 is a more sensitive lineage marker than SOX10 in MBC, SOX10 is a useful adjunct because it is positive in most GATA3-negative breast metastases. Using both GATA3 and SOX10 is recommended for confirming breast as the site of origin in metastases that lack estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 expression, whereas the addition of AR is not helpful.

Cytokeratin 7, inhibin, and p63 in testicular germ cell tumor: superior markers of choriocarcinoma compared to ß-human chorionic gonadotropin.

Choriocarcinoma can be difficult to differentiate from other subtypes of testicular germ cell tumor and can occur unexpectedly in a distant, late metastasis. The aim of this investigation was to identify a marker superior to ß-human chorionic gonadotropin (ß-hCG) for choriocarcinoma. Sixty-two primary and metastatic testicular germ cell tumors (27 choriocarcinomas, 19 yolk sac tumors, 29 embryonal carcinomas, 28 seminomas, 22 teratomas, 3 epithelioid trophoblastic tumors [ETTs]) were analyzed for immunohistochemical expression of cytokeratin 7 (CK7), inhibin, p63, and ß-hCG. All choriocarcinomas and ETTs were strongly positive for CK7, whereas seminomas were negative and 52% of embryonal carcinomas had weak reactivity. Eighty-four percent of yolk sac tumors and 59% of teratomas were CK7 positive. Eighty-nine percent of choriocarcinomas and 100% of ETTs were positive for inhibin, with reactivity highlighting syncytiotrophoblasts, whereas seminomas, embryonal carcinomas, yolk sac tumors, and teratomas were negative. Eighty-five percent of choriocarcinomas expressed p63, with staining mostly in mononucleated trophoblasts, whereas seminomas, embryonal carcinomas, and yolk sac tumors were negative. Teratomas expressed p63 in 32% of cases. ß-hCG was reactive in 96% of choriocarcinomas, 33% of ETTs, 46% of seminomas, 54% of embryonal carcinomas, 47% of yolk sac tumors, and 32% of teratomas. ß-hCG staining within other subtypes was more likely if choriocarcinoma was present elsewhere in the tumor (P = .0002). CK7 is a highly sensitive marker for choriocarcinoma and differentiates choriocarcinoma from seminoma and embryonal carcinoma. Inhibin and p63 are sensitive and specific for choriocarcinoma versus seminoma, embryonal carcinoma, and yolk sac tumor. To identify choriocarcinoma, CK7, inhibin, and p63 are superior to ß-hCG.

Initial diagnosis of insignificant cancer, high-grade prostatic intraepithelial neoplasia, atypical small acinar proliferation, and negative have the same rate of upgrade to a Gleason score of 7 or higher on repeat prostate biopsy.

Extended prostate needle core biopsies are standard of care for the diagnosis of prostatic carcinoma. Subsequent biopsies may be performed for a variety of indications. Knowledge of biopsy characteristics indicating risk for progression may have utility to guide therapeutic management. Prostate needle core biopsies performed between 2008 and 2014 were reviewed. Patients with at least 1 subsequent biopsy were identified. Cases were categorized by worst initial diagnosis. Gleason ≤6 carcinoma was further classified as significant or insignificant with insignificant defined as follows: ≤2 cores with carcinoma, sites with ≤50% carcinoma, and unilateral carcinoma. A total of 329 men underwent repeat biopsies. Gleason ≤6 insignificant carcinoma, high-grade prostatic intraepithelial neoplasia (HGPIN) and/or atypical small acinar proliferation, and negative biopsies had a similar rate of Gleason ≥7 upon repeat biopsy (16%, 17%, 14%; P = .91). Initial biopsy diagnoses of Gleason ≤6 significant carcinoma had a higher rate of Gleason ≥7 on repeat biopsy compared with initial biopsies of Gleason ≤6 insignificant carcinoma (39%, 16%; P = .003). Within initial diagnoses of Gleason ≤6, 1 core compared with more than 1 core positive had a lower rate of Gleason ≥7 on repeat biopsy (17%, 30%), although this difference was not significant (P = .08). An initial biopsy diagnosed as Gleason ≤6 insignificant carcinoma, HGPIN and/or atypical small acinar proliferation, or negative had a similar substantial risk of Gleason ≥7 carcinoma upon subsequent biopsy. Our findings support the continued stratification of Gleason ≤6 and thus the diagnostic workup of all atypical foci to provide an accurate, thorough number of involved cores.