Metastases to the kidney: a clinicopathological study of 43 cases with an emphasis on deceptive features.

AIMS: To review our experience with metastases to the kidney in surgical pathology material. METHODS AND RESULTS: The clinicopathological features of all metastases to the kidney in surgical pathology cases between May 1987 and May 2013 at our institution were reviewed. Autopsy cases were excluded. Forty-three cases (16 nephrectomies, 25 biopsies, and two fine needle aspirations) were included; the primary malignancy was diagnosed prior to/concurrently with the metastasis in nearly all cases. Common primary sites included the lung, breast, female genital tract, and head and neck; the majority were carcinomas. A primary renal tumour was suspected prior to the pathological diagnosis in 35% of cases. Unusual features included: common unilateral (77%) and unifocal (70%) involvement, lack of other distant organ metastases (37%), >10 years between primary and metastasis diagnoses (19%), lack of a discrete mass (5%), and renal vein extension (19% of resections). The most common dilemma was excluding urothelial or high-grade renal cell carcinoma; however, metastases from the thyroid commonly mimicked low-grade renal cell carcinomas. CONCLUSIONS: In surgical pathology material, metastases to the kidney most commonly present as solitary unilateral masses, and in a substantial subset of cases mimic a primary renal tumour.

Renal vein leiomyosarcoma: imaging and clinical features of a renal cell carcinoma mimic.

Renal vein leiomyosarcoma is a rare tumor whose clinical and imaging features can significantly overlap with those of advanced primary renal neoplasms, particularly renal cell carcinoma. IRB approval was obtained for a retrospective review of clinical and imaging information for five patients with the pathologically proven diagnosis of renal vein leiomyosarcoma at two institutions. Among the five patients, two were female and three male; average age 58.6 (range 42-77). Three patients presented with flank or abdominal pain, one with pulmonary embolism, and one with weight loss and fatigue. Mass size ranged from 4 to 10 cm. Four masses were left-sided and one right-sided. Tumors involved and expanded the renal vein in all cases, with tumor extension to the renal hilum in one case, through the renal hilum into renal parenchyma in two cases, and into inferior vena cava in two cases. All masses demonstrated contrast enhancement, which was solely peripheral in one case. In all cases, extrarenal tumor volume was greater than renal parenchymal tumor volume. When renal masses are predominantly or exclusively intravascular, consideration should be given to the diagnosis of renal vein leiomyosarcoma because preoperative biopsy results could significantly alter management.

Partial atrophy in prostate needle biopsies: a detailed analysis of its morphology, immunophenotype, and cellular kinetics.

We systematically analyzed 73 prospectively collected partial atrophy (PA) foci from over 185 prostate needle biopsy cases to characterize them along 3 fronts: morphologic, as it can be a mimic of prostate cancer (PCa), immunohistochemical (basal cell markers and alpha-methyl acyl-CoA racemase), as it often shares the staining characteristics of PCa, and cellular kinetics (MIB-1 proliferation marker), as it belongs to the larger group of focal atrophy, some of which have been shown to be proliferative and associated with chronic inflammation. The following morphologic features were prominent at low magnification: small to mid-sized glands with circumscribed (70%) or disorganized growth pattern (30%), presence of stellate/undulated gland lumina (92%), associated few completely atrophic glands within the PA focus (97%), and scant apical but abundant lateral pale/clear cytoplasm similar to adjacent benign glands (100%). On higher magnification, 33% of foci contained micronucleoli, but all lacked nuclear enlargement (100%) or macronucleoli (100%), characteristic of PCa. No adjunctive features of PCa were seen. Patchy basal cell staining was observed in 52/71 (73%), whereas 4/71 (6%) were completely negative. alpha-methyl acyl-CoA racemase demonstrated variable expression, stronger than the benign glands in 7/72 (10%) foci. Associated pathology included PCa (42%), and complete atrophy (91%), distinct from PA foci. There was no difference between the mean proliferative index of the PA foci compared with the benign glands [5.5 (range 0 to 30) and 5.6 (range 0 to 31), respectively, P=0.97 by paired t test], as measured quantitatively by ChromaVision system. PA foci were rarely associated with inflammation (1%). Familiarity with these morphologic features and staining characteristics will allow its confident separation from cancer, especially in limited biopsy material. PA foci do not represent a spectrum of proliferative inflammatory atrophy, justifying its term.

Drug-associated histiocytoid Sweet's syndrome: a true neutrophilic maturation arrest variant.

Histiocytoid Sweet's syndrome is a recently described entity which has clinical features identical to typical Sweet's syndrome but is distinguished by a dermal cellular infiltrate composed not of mature neutrophils but of immature granulocytes. Herein, we report a case of bone marrow granulocytic maturation arrest and a histological histiocytoid Sweet's-like reaction pattern following trimethoprim-sulfamethoxazole therapy.

Wagner-Meissner neurilemmoma of the right cheek.

We report a very rare case of Wagner-Meissner neurilemmoma in the cheek of a 10-year-old boy. The tumor presented as a slowly growing soft tissue swelling. Magnetic resonance imaging disclosed a very infiltrative, 9-cm mass involving the subcutis and deep soft tissues of the right cheek. Microscopically, the tumor was unencapsulated and composed almost entirely of well-formed Wagner-Meissner corpuscles that formed confluent sheets, perivascular cuffs, and individual corpuscles percolating through adipose tissue. Compared with the 3 previous reports, which describe circumscribed, encapsulated tumors in adult patients, this case had distinctive clinicopathologic features never reported: presentation in a pediatric patient, location in the head and neck region, and an infiltrative growth pattern.

Outcomes of benign intraductal papillomas diagnosed on core biopsy: a review of 104 cases with subsequent excision from a single institution.

A diagnosis of papilloma with atypia on core biopsy (CB) requires excision, as the risk of associated malignancy is high (average 36.9%). The management of benign intraductal papillomas (IP) diagnosed on CB is controversial due to varying upgradation rates (0-29%, average 7%) reported on excision. Our aim was to study the clinical, radiological, and pathological features associated with benign IP upgradation at our institution. An electronic data base search (keyword papilloma), from Jan. 2000-Aug. 2015 identified 258 CBs. After exclusions, 104 CBs of benign IPs with subsequent excisions from 101 females were reviewed. The clinical, radiological, and pathological features between IPs that had upgrades (defined as malignancy or atypical ductal hyperplasia) and non-upgraded IPs were compared using descriptive statistics. Studies of benign IP on CB with at least 50 follow-up excisions published between 2008 and 2016 were analyzed. Residual IP was present in 83.6% (87/104) of reviewed excisions. There were six upgrades (5.6%) (4 to malignancy (3.8%) and 2 to atypical ductal hyperplasia).Upgrades were associated with mass on imaging with a trend to significance (p = .05). Two cases with malignant upgrade had a history of contralateral cancer. An analysis of 25 published studies showed an average malignant upgrade of 5.7% (182/3164). The majority of benign IP are not upgraded on excision; thus, not all need to be excised. Those that may warrant excision are those with prior history of carcinoma, those with a mass on imaging, and/or suboptimal or imaging-discordant CB sampling.

Categorizing renal oncocytic neoplasms on core needle biopsy: a morphologic and immunophenotypic study of 144 cases with clinical follow-up.

There is limited literature on renal oncocytic neoplasms diagnosed on core biopsy. All renal oncocytic neoplasm core biopsies from 2006 to 2013 were retrospectively reviewed. Morphologic features and an immunohistochemical panel of CK7, c-KIT, and S100A1 were assessed. Concordance with resection diagnosis, statistical analysis including a random forest classification, and follow-up were recorded. The post-immunohistochemical diagnoses of 144 renal oncocytic core biopsies were favor oncocytoma (67%), favor renal cell carcinoma (RCC) (12%), and cannot exclude RCC (21%). Diagnosis was revised following immunohistochemistry in 7% of cases. The most common features for oncocytoma (excluding dense granular cytoplasm) were nested architecture, edematous stroma, binucleation and tubular architecture; the most common features for favor RCC were sheet-like architecture, nuclear pleomorphism, papillary architecture, and prominent cell borders. High nuclear grade, necrosis, extensive papillary architecture, raisinoid nuclei, and frequent mitoses were not seen in oncocytomas. Comparing the pathologist and random forest classification, the overall out-of-bag estimate of classification error dropped from 23% to 13% when favor RCC and cannot exclude RCC were combined into 1 category. Resection was performed in 19% (28 cases) with a 94% concordance (100% of favor RCC biopsies and 90% of cannot exclude RCC biopsies confirmed as RCC; 83% of favor oncocytomas confirmed); ablation in 23%; and surveillance in 46%. Follow-up was available in 92% (median follow-up, 33months) with no adverse outcomes. Renal oncocytic neoplasms comprise a significant subset (16%) of all core biopsies, and the majority (78%) can be classified as favor oncocytoma or favor RCC.

Clinicopathologic characteristics of anterior prostate cancer (APC), including correlation with previous biopsy pathology.

Anterior-predominant prostate cancer (APC) is an incompletely understood entity which can be difficult to sample via transrectal biopsy. Seemingly favorable biopsy results may belie the potential aggressiveness of these tumors. Here, we attempt to characterize APC by retrospectively examining the clinicopathologic features of APC at radical prostatectomy and comparing our findings with prior biopsy information. We found that 17.4 % of patients in our study had APC. APC demonstrated a significantly lower (P value < 0.05) Gleason score (GS) and pathologic stage than non-APC tumors, including the absence of seminal vesicle invasion by APC. A subset (5.6 %) of APC consisted of high-grade tumors (GS ≥ 8), and these tumors were more often detected on transperineal saturation biopsy than non-transperineal saturation (i.e., transrectal ultrasound guided) biopsy strategies. Four patients (7 %) without transperineal saturation biopsy exhibited a significantly worse GS at RP than biopsy, compared to five patients (36 %) with transperineal saturation biopsy. Our findings corroborate the difficulty in detecting APC and suggest that APC is not a uniform disease with a wholly indolent phenotype. Dedicated long-term outcome data are needed in these patients. Additionally, alternative pathologic staging parameters may be necessary.

Impact of tertiary Gleason pattern 5 on prostate cancer aggressiveness: Lessons from a contemporary single institution radical prostatectomy series.

OBJECTIVE: To better evaluate tertiary Gleason pattern reporting and to evaluate the impact of tertiary Gleason pattern 5 (TP5) on prostate cancer pathological features and biochemical recurrence at our large single institution. METHODS: We retrospectively reviewed 1962 patients who underwent radical prostatectomy (RP) for prostate cancer; TP5 was reported in 159 cases (8.1%). Men with Gleason score (GS) 7 and GS 8 disease were divided into subgroups with and without TP5, and histopathological features were compared. Multivariate analyses were conducted to assess the impact on TP5 on biochemical-free survival (BFS). RESULTS: Tumors possessing GS 3 + 4 with TP5 were more likely to exhibit extraprostatic extension (EPE) and had a larger tumor diameter (TD) than GS 3 + 4 alone. GS 3 + 4 with TP5 was also associated with positive surgical margins (SM), seminal vesicle involvement (SVI), and higher pre-operative prostate-specific antigen (PSA) values, but without statistical significance. GS 4 + 3 with TP5 more commonly presented with EPE, positive SM, SVI, and greater TD and pre-operative PSA level than GS 4 + 3 alone. In multivariate analysis, Gleason score, EPE, and TP5 were overall independent risk factors for PSA recurrence in this cohort. Additionally, GS 4 + 3 with TP5 was associated with shorter time to recurrence versus GS 4 + 3 alone. CONCLUSION: Our results emphasize the importance of TP5 and suggest that criteria for tertiary pattern reporting in prostate cancer should be standardized. Further studies are needed to evaluate the role of tertiary patterns in prognostic models.

Is intraoperative frozen section analysis of reexcision specimens of value in preventing reoperation in breast-conserving therapy?

OBJECTIVES: A prior study at our institution showed a marked reduction in reoperation for margin reexcision following the development of an intraoperative frozen section evaluation of margins (FSM) practice on lumpectomy specimens from patients undergoing breast-conserving therapy (BCT). This study aimed to examine the frequency of FSM utilization, FSM pathology performance, and outcomes for BCT patients undergoing margin reexcision only. METHODS: Consecutive reexcision-only specimens were reviewed from a 40-month period following the development of the FSM practice. Clinicopathologic features and patient outcomes were assessed. RESULTS: FSM was performed in 46 (30.7%) of 150 reexcision-only operations. Of the 46 operations with FSM, there were 28 (60.9%) true-negative, 12 (26.1%) true-positive, six (13.0%) false-negative, and no false-positive cases. There was no difference in further reexcision, total operations, or conversion to mastectomy among patients with and without FSM. Need for further reexcision was significantly associated with tumor multifocality (P = .008). CONCLUSIONS: Despite overall good pathology performance for FSM in reexcision-only specimens, use of FSM did not affect patient outcome. Rather, underlying disease biology appeared most significant in predicting whether adequate surgical margins could be attained.

Intraoperative frozen section analysis of margins in breast conserving surgery significantly decreases reoperative rates: one-year experience at an ambulatory surgical center.

Intraoperative frozen section (FS) margin evaluation is not common practice for patients undergoing breast conservation therapy (BCT), but offers a significant reduction in reoperation. In this study, a technique to allow for more effective freezing of breast tissue was developed to perform FS evaluation of lumpectomy margins (FSM) for all patients undergoing BCT at an ambulatory surgery center. FS evaluation of sentinel lymph node biopsy specimens was performed concurrently. One hundred eighty-one study and 188 control patients, with and without FS evaluation, were compared. Reexcision was reduced 34% (from 48.9% to 14.9%) and reoperation was reduced 36% (from 55.3% to 19.3%) with FS evaluation. Most of the decrease in reoperative rate was because of a decrease in the need for margin reexcision. The number of patients requiring 1, 2, or 3 operations to complete therapy was 84, 92, and 12, respectively, in the control group, and 146, 33, and 2, respectively, in the study group. Lobular subtype, multifocal disease, and larger tumor size (≥2 cm) were significantly associated with failure of FSM to prevent reoperation, but reoperation rates were still significantly decreased in this subgroup of patients (from 75.5% to 43.8%) with FSM. This study highlights an innovative yet simple and adaptable FS approach that resulted in a nearly 3-fold reduction in reoperation for patients undergoing BCT.

Response to a lethal dose of heat shock by a transient up-regulation of clusterin expression followed by down-regulation and apoptosis in prostate and bladder cancer cells.

BACKGROUND: Clusterin is a ubiquitous, secretory glycoprotein with a wide array of functions. Recent studies have implicated that clusterin functioned as heat shock response proteins. The objective of the present study was to determine the fate of clusterin expression in cancer cells, which were subjected to a lethal dose of heat shock, in an attempt to shed light on mechanisms of action of clusterin. METHODS: A prostate cancer line, PC-3, and a bladder cancer line, TSU-Pr1, were selected owing to their aggressive growth behaviors. Apoptosis was assessed by enzymatic activities of terminal deoxynucleotidyl transferase as well as by activities of caspase-3. Cells were exposed to 45 degrees C for a period of 60 min. RESULTS: Both cell lines underwent a transient up-regulation of clusterin expression followed by down-regulation and apoptosis. TSU-Prl cells produced higher levels of clusterin and displayed a greater resistance to apoptosis than did PC-3 cells. The addition of exogenous clusterin to the cultures of PC-3 cells protected apoptosis. Treatment of oligonucleotide antisense to clusterin to the cultures of TSU-Pr1 cells enhanced apoptosis mediated by heat shock. CONCLUSION: Clusterin offers a protection to PC-3 and TSU-Prl cells against heat shock and plays an important role in the cascade of events initiated by heat shock. Prostate 53: 277-285, 2002.