Impact of genomic testing on urologists' treatment preference in favorable risk prostate cancer: A randomized trial.

INTRODUCTION: The Oncotype Dx Genomic Prostate Score (GPS) is a 17-gene relative expression assay that predicts adverse pathology at prostatectomy. We conducted a novel randomized controlled trial to assess the impact of GPS on urologist's treatment preference for favorable risk prostate cancer (PCa): active surveillance versus active treatment (i.e., prostatectomy/radiation). This is a secondary endpoint from the ENACT trial which recruited from three Chicago hospitals from 2016 to 2019. METHODS: Ten urologists along with men with very low to favorable-intermediate risk PCa were included in the study. Participants were randomly assigned to standardized counseling with or without GPS assay. The main outcome was urologists' preference for active treatment at Visit 2 by study arm (GPS versus Control). Multivariable best-fit binary logistic regressions were constructed to identify factors independently associated with urologists' treatment preference. RESULTS: Two hundred men (70% Black) were randomly assigned to either the Control (96) or GPS arm (104). At Visit 2, urologists' preference for prostatectomy/radiation almost doubled in the GPS arm to 29.3% (29) compared to 14.1% (13) in the Control arm (p = 0.01). Randomization to the GPS arm, intermediate NCCN risk level, and lower patient health literacy were predictors for urologists' preference for active treatment. DISCUSSION: Limitations included sample size and number of urologists. In this study, we found that GPS testing reduced urologists' likelihood to prefer active surveillance. CONCLUSIONS: These findings demonstrate how obtaining prognostic biomarkers that predict negative outcomes before treatment decision-making might influence urologists' preference for recommending aggressive therapy in men eligible for active surveillance.

Surgical management of locally invasive basaloid carcinoma of thymic gland.

Thymic basaloid carcinoma is an extremely rare thymic tumor variant, and the most common presentations have been an incidental finding on a routine chest X-ray and dyspnea on exertion. Given its rarity, no treatment modalities have been demonstrated to improve survival. This rare case describes a patient with locally advanced thymic basaloid carcinoma treated by en bloc resection of phrenic nerve and left upper lobe with the tumor followed by adjuvant radiation therapy. Patient had no respiratory complaints at 10 months follow-up, and 10-month post-operative surveillance radiological study showed no objective sign of tumor recurrence.

Impact of a Genomic Test on Treatment Decision in a Predominantly African American Population With Favorable-Risk Prostate Cancer: A Randomized Trial.

PURPOSE: The Genomic Prostate Score (GPS), performed on biopsy tissue, predicts adverse outcome in prostate cancer (PCa) and has shown promise for improving patient selection for active surveillance (AS). However, its impact on treatment choice in high-risk populations of African Americans is largely unknown and, in general, the effect of the GPS on this difficult decision has not been evaluated in randomized trials. METHODS: Two hundred men with National Comprehensive Cancer Network very low to low-intermediate PCa from three Chicago hospitals (70% Black, 16% college graduates) were randomly assigned at diagnosis to standard counseling with or without a 12-gene GPS assay. The primary end point was treatment choice at a second postdiagnosis visit. The proportion of patients choosing AS was compared, and multivariable modeling was used to estimate the effects of various factors on AS acceptance. RESULTS: AS acceptance was high overall, although marginally lower in the intervention group (77% v 88%; P = .067), and lower still when men with inadequate specimens were excluded (P = .029). Men with lower health literacy who received a GPS were seven-fold less likely to choose AS compared with controls, whereas no difference was seen in men with higher health literacy (Pinteraction = .022). Among men with low-intermediate risk, 69% had GPS values consistent with unfavorable intermediate or high-risk cancer. AS choice was also independently associated with a family history of PCa and having health insurance. CONCLUSION: In contrast to other studies, the net effect of the GPS was to move patients away from AS, primarily among men with low health literacy. These findings have implications for our understanding of how prognostic molecular assays that generate probabilities of poor outcome can affect treatment decisions in diverse clinical populations.

Alpha-methylacyl-CoA racemase (AMACR/P504S) can distinguish hepatocellular carcinoma and dysplastic hepatocytes from benign nondysplastic hepatocytes.

Immunohistochemical staining with alpha-methylacyl-CoA racemase AMACR (P504S) has been described in a number of normal tissues and was found to be useful for detecting malignancies including hepatocellular carcinoma (HCC). Our aim was to determine whether AMACR is differentially expressed in benign nondysplastic liver tissue, hepatocellular dysplasia, and HCC. The study material consisted of paraffin blocks containing primary HCC and surrounding liver tissue from 20 patients who underwent hepatectomy at the time of liver transplantation. Immunohistochemical stains were performed with anti-AMACR by standard methods. Staining features were characterized on the basis of the pattern and distribution of reactivity. A positive AMACR immunostain was defined as either finely stippled or coarsely granular in pattern, in a diffuse or parabasal cytoplasmic distribution. A negative AMACR immunostain was defined as absence of reactivity. Anti-AMACR immunostains were positive in malignant, dysplastic, and benign nondyplastic hepatocytes in all cases. The staining pattern was the same in malignant and dysplastic hepatocytes. It consisted of coarsely granular reactivity in a parabasal or diffuse cytoplasmic distribution. In contrast, benign nondysplastic hepatocytes were distinguished by weak, finely stippled diffuse cytoplasmic staining. Malignant and dysplastic hepatocytes showed an identical pattern of immunostaining for AMACR that was distinct from benign hepatocytes. Prospective studies are needed to determine whether staining for AMACR can distinguish HCC or dysplasia in cytologic and small histologic specimens.

Fine-needle aspiration biopsy of cystic pleomorphic adenoma with adnexa-like differentiation mimicking mucoepidermoid carcinoma: a case report.

Although pleomorphic adenomas (PAs) usually can be diagnosed very accurately with fine-needle aspiration biopsy (FNAB), even this common salivary gland neoplasm can be diagnostically challenging and cause pitfalls in cytodiagnosis. In particular, the presence of either cystic changes or squamous, mucinous, or sebaceous metaplasia can lead to a false positive diagnosis of mucoepidermoid carcinoma (MEC). Here, we present a case of a 70-yr-old man with an asymptomatic left deep lobe parotid mass for which CT-guided FNAB was performed. The FNAB cytology revealed cohesive clusters of squamous epithelial cells, sebaceous cells, oncocytes, macrophages, and rare myoepithelial cells. Characteristic metachromatic fibrillar chondromyxoid stroma, which usually is seen in PAs, was not seen in the aspirate. Although cytodiagnosis of PAs was suggested based on the presence of other cellular components, resection was recommended. The subsequent parotidectomy specimen revealed an encapsulated cystic PA with mixed appendageal differentiation including areas of squamous, mucinous, sebaceous, and oncocytic metaplasia. Chondromyxoid stroma was only focally present. Presence of squamous, mucinous, and/or sebaceous metaplasia, especially in the absence of chondromyxoid stroma, presents the potential for misinterpretation of the FNAB as indicative of malignancy in general and MEC in particular.

Primary Ureteral Thyroid Transcription Factor 1-Positive Small Cell Neuroendocrine Carcinoma: Case Report and Review of the Literature.

Upper urinary tract neoplasms comprise only 5% of urinary malignancies overall, the overwhelming majority showing an urothelial histology. Nonurothelial lesions represent 1.9% of upper tract neoplasms, and small cell carcinomas (SmCCs) only account for a minute fraction of them, with few cases reported in the literature to date. In the genitourinary tract, these lesions are most frequently found in the urinary bladder, where they tend to show a mixed histology with a characteristic small cell neuroendocrine component that is positive for chromogranin A, synaptophysin, and CD56 immunostains. Urinary SmCCs are almost invariably aggressive, with a propensity to infiltrate surrounding tissues and vascular structures. Unfortunately, clinical stage at presentation is often advanced, with early dissemination to lymph nodes or distant organs in a significant proportion of patients. For the most part, prognosis is dismal and can be predicted by the pathologic stage at diagnosis. Recently, new chemotherapeutic regimens have shown some potential benefit for the treatment of urinary SmCC, albeit not achieving curative results. Here we present the case of a 71-year-old male patient with a history of treated bladder urothelial carcinoma that presented with subacute flank pain and was diagnosed with a primary pure SmCC of the ureter. Besides the usual neuroendocrine immunomarkers, this tumor showed intense positivity for TTF-1 (thyroid transcription factor-1), a phenomenon that has been described for extrapulmonary SmCC of other locations.

Follicular lesions of the thyroid: a retrospective study of 1,348 fine needle aspiration biopsies.

Fine needle aspiration (FNA) has proven to be an effective tool in management of patients with thyroid nodules. However, the diagnosis of follicular patterned lesions can be challenging. The surgical and cytopathology computer database at a large referral medical center was searched for cases that had both cytologic and histologic thyroid accessions from January 2004 to November 2008. A total of 1,255 histologic thyroid specimens and 2,776 thyroid FNA biopsies were retrieved for review. Histologically, 272 overt malignancies were identified; 20 (7.4%) were follicular carcinomas. Cytologically, 1,348 cases were follicular-patterned lesions, comprising 1,044 cases of "benign follicular nodules" (BFN), 137 cases of "follicular lesions of undetermined significance" (FLUS), and 167 cases of "suspicious for follicular neoplasm" (SFN). Seventy-nine (7.5%) of BFN, 23 (16.8%) of FLUS, and 65 (38.9%) of SFN cases had histologic follow-up. Overt malignancy, a cystic papillary carcinoma, was identified histologically in only one case of BFN, for a negative predictive value of 98.7%. Overt malignancy was identified histologically in two cases of FLUS, both follicular variant of papillary carcinoma, for a positive predictive value of 8.7%. Overt malignancy was identified histologically in 14 cases of SFN, for a positive predictive value of 21.5%. Five follicular carcinomas were identified histologically in the SFN category, all minimally invasive. Incidental ("occult") papillary microcarcinoma were identified histologically in all three categories. In this study, the risk of overt malignancy increases from 1.3%, to 8.7%, to 21.5% for BFN, FLUS, and SFN, respectively. All follicular carcinomas identified histologically occurred in the SFN category and all were minimally invasive. Papillary microcarcinomas can occur in any of the three diagnostic categories.

Biatrial primary synovial sarcoma of the heart.

Synovial sarcomas that primarily arise from the heart and pericardium are extremely rare, especially the ones involving both sides of the heart. To date, few cases have been reviewed in the literature. Our patient was a 36-year-old man who presented with primary biatrial synovial sarcoma that also involved the tricuspid annulus, heart valves, and interatrial septum. The tumor was debulked to relieve the atrioventricular obstruction. Molecular analysis confirmed the diagnosis of synovial sarcoma with positive t (X;18) SYT-SSX gene fusion. The patient is currently receiving chemotherapy. From our review of the 20 cases thus far reported in the English-language medical literature, the tumor more frequently affects young male patients, and carries a poor prognosis. Early detection is difficult because of the aggressive nature of the tumor. Like other sarcomas, wide surgical resection remains the mainstay of therapy. Adjuvant radiation therapy for local recurrence and chemotherapy for control of systemic disease may have some beneficial effect on overall survival, but the benefit is likely limited.