Search

Renal oncocytoma (RO) accounts for 5% of renal cancers and generally behaves as a benign tumor with favorable long-term prognosis. It is difficult to confidently distinguish between benign RO and other renal malignancies, particularly chromophobe renal cell carcinoma (chRCC). Therefore, RO is often managed aggressively with surgery. We sought to identify molecular biomarkers to distinguish RO from chRCC and other malignant renal cancer mimics. In a 44-patient discovery cohort, we identified a significant differential abundance of nine genes in RO relative to chRCC. These genes were used to train a classifier to distinguish RO from chRCC in an independent 57-patient cohort. The trained classifier was then validated in five independent cohorts comprising 89 total patients. This nine-gene classifier trained on the basis of differential gene expression showed 93% sensitivity and 98% specificity for distinguishing RO from chRCC across the pooled validation cohorts, with a c-statistic of 0.978. This tool may be a useful adjunct to other diagnostic modalities to decrease the diagnostic and management uncertainty associated with small renal masses and to enable clinicians to recommend more confidently less aggressive management for some tumors. PATIENT SUMMARY: Renal oncocytoma is generally a benign form of kidney cancer that does not necessarily require surgical removal. However, it is difficult to distinguish renal oncocytoma from other more aggressive forms of kidney cancer, so it is treated most commonly with surgery. We built a classification tool based on the RNA levels of nine genes that may help avoid these surgeries by reliably distinguishing renal oncocytoma from other forms of kidney cancer.

Context.-Since 2016, transoral endoscopic thyroid resection with vestibular approach (TOETVA) has been increasingly performed in the United States. Although guidelines for the procedure are evolving, indeterminate and malignant preoperative cytopathologic diagnoses are not a contraindication. There are limited data related to the pathologic examination of these specimens. Objective.-To examine the clinicopathologic features of TOETVA specimens with particular attention to limitations of interpretation of pathologic parameters and final diagnosis. Design.-We reviewed age, sex, preoperative imaging and cytologic diagnoses, surgical pathology, and clinical follow-up data in TOETVA resections from our institution for procedures performed between March 2016 and December 2019. Results.-Fifty cases of TOETVA were identified, comprising 48 women and 2 men with a mean age of 47 years. Preoperative cytologic diagnoses were available in 47 cases and included 19 nondiagnostic/benign (Bethesda I/ II), 24 follicular lesion of undetermined significance/ suspicious for follicular neoplasm (Bethesda IIl/lV), and 4 suspicious/malignant diagnoses (Bethesda V/VI). Thirtyfour cases (68%) among the surgical resection specimens showed disruption and/or fragmentation. Thirty-nine cases were negative for carcinoma, including hyperplasias and benign/indolent neoplasms. Eleven cases exhibited papillary thyroid carcinoma. Final diagnoses were reached in all disrupted/fragmented cases. In 2 cases of papillary thyroid carcinoma, tumor size, microscopic extrathyroidal extension, and margin status could not be determined. Conclusions.-A significant proportion of TOETVA specimens are disrupted/fragmented, which can compromise information about tumors, including size, number, margin status, and microscopic extrathyroidal extension. Given that these parameters inform treatment and followup, this should be considered when selecting patients for TOETVA., Transoral endoscopic thyroid resection with vestibular approach (TOETVA) has become increasingly available in the surgical management of both neoplastic and nonneoplastic thyroid conditions in the past decade. (1) Briefly, the [...]

The presence of sarcomatoid features in clear cell renal cell carcinoma (ccRCC) confers a poor prognosis and is of unknown pathogenesis. We performed exome sequencing of matched normal-carcinomatous-sarcomatoid specimens from 21 subjects. Two tumors had hypermutation consistent with mismatch repair deficiency. In the remainder, sarcomatoid and carcinomatous elements shared 42% of somatic single-nucleotide variants (SSNVs). Sarcomatoid elements had a higher overall SSNV burden (mean 90 vs. 63 SSNVs, P = 4.0 × 10(-4)), increased frequency of nonsynonymous SSNVs in Pan-Cancer genes (mean 1.4 vs. 0.26, P = 0.002), and increased frequency of loss of heterozygosity (LOH) across the genome (median 913 vs. 460 Mb in LOH, P < 0.05), with significant recurrent LOH on chromosomes 1p, 9, 10, 14, 17p, 18, and 22. The most frequent SSNVs shared by carcinomatous and sarcomatoid elements were in known ccRCC genes including von Hippel-Lindau tumor suppressor (VHL), polybromo 1 (PBRM1), SET domain containing 2 (SETD2), phosphatase and tensin homolog (PTEN). Most interestingly, sarcomatoid elements acquired biallelic tumor protein p53 (TP53) mutations in 32% of tumors (P = 5.47 × 10(-17)); TP53 mutations were absent in carcinomatous elements in nonhypermutated tumors and rare in previously studied ccRCCs. Mutations in known cancer drivers AT-rich interaction domain 1A (ARID1A) and BRCA1 associated protein 1 (BAP1) were significantly mutated in sarcomatoid elements and were mutually exclusive with TP53 and each other. These findings provide evidence that sarcomatoid elements arise from dedifferentiation of carcinomatous ccRCCs and implicate specific genes in this process. These findings have implications for the treatment of patients with these poor-prognosis cancers.

* In this short review, we discuss primary diffuse large B-cell lymphoma of the testis, an entity that is most commonly seen in older patients. The most common clinical presentation is a unilateral testicular mass. Microscopically, the tumor shows diffuse infiltration of lymphocytes between intact seminiferous tubules. Spermatogenic arrest, interstitial fibrosis, and tubular hyalinization are commonly seen. The tumor is positive for B-cell markers by immunohistochemistry. Treatment has traditionally been with orchiectomy and combination chemotherapy; however, only a minority of patients enjoy a prolonged disease-free survival. Differential diagnosis includes seminoma and viral and granulomatous orchitis. doi:10.5858/arpa.2010-0158-RS, Primary testicular lymphoma is a collection of neoplasms that comprises only 1% to 9% of testicular neoplasms. However, it is the most common malignant testicular tumor in men older than [...]

* In this short review, we discuss clear cell adenocarcinoma of the urinary bladder, a rare tumor that primarily affects women. The histogenesis of this neoplasm is uncertain; in some tumors the clinicopathologic and histologic features are suggestive of a mullerian origin. Clear cell adenocarcinoma consists of cells with abundant clear cytoplasm, arranged in solid, glandular, or tubulocystic patterns. These tumors are positive for pancytokeratin, cytokeratin 7, and CA 125 immunohistochemical stains. Patients typically present with gross hematuria, dysuria, and discharge. The natural history is poorly understood and patient outcomes remain unclear. Currently, surgery is the treatment of choice. Nephrogenic adenoma is the most important differential diagnostic consideration, followed by metastatic clear cell carcinoma., Clear cell adenocarcinoma (CCA) usually arises from the female genital tract. However, CCA is sometimes found in the lower urinary tract in women, most commonly involving the urethra, (1) where [...]

* Amnion nodosum is commonly regarded as a placental hallmark of severe and prolonged oligohydramnios. It consists of nodules of amorphous granular material present on the surface of the amnion. We reviewed all 45 cases of amnion nodosum from our placental database from 1994 through 2003 (study group). The control group consisted of 45 cases from the same database matched for gestational age but without amnion nodosum. Oligohydramnios, multiple pregnancy, perinatal mortality, macerated stillbirths, and chronic twin-twin transfusion were the most common clinical features encountered in the study group. Luminal vascular abnormalities of chorionic villi, fibrosis of chorionic villi, and placental edema were the placental features that were more frequently present in the study group. (Arch Pathol Lab Med. 2007;131:1829-1833), Amnion nodosum (AN) is a placental lesion consisting of numerous small nodules on the amnion of the chorionic disc, placental membranes, or the umbilical cord. Prior to 1950 when Landing [...]

The presence of sarcomatoid features in clear cell renal cell carcinoma (ccRCC) confers a poor prognosis and is of unknown pathogenesis. We performed exome sequencing of matched normal-carcinomatous- sarcomatoid specimens from 21 subjects. Two tumors had hypermutation consistent with mismatch repair deficiency. In the remainder, sarcomatoid and carcinomatous elements shared 42% of somatic single-nucleotide variants (SSNVs). Sarcomatoid elements had a higher overall SSNV burden (mean 90 vs. 63 SSNVs, P = 4.0 × 10-4), increased frequency of nonsynonymous SSNVs in Pan- Cancer genes (mean 1.4 vs. 0.26, P = 0.002), and increased frequency of loss of heterozygosity (LOH) across the genome (median 913 vs. 460 Mb in LOH, P < 0.05), with significant recurrent LOH on chromosomes 1p, 9, 10, 14, 17p, 18, and 22. The most frequent SSNVs shared by carcinomatous and sarcomatoid elements were in known ccRCC genes including von Hippel-Lindau tumor suppressor (VHL), polybromo 1 (PBRM1), SET domain containing 2 (SETD2), phosphatase and tensin homolog (PTEN). Most interestingly, sarcomatoid elements acquired biallelic tumor protein p53 (TP53) mutations in 32% of tumors (P = 5.47 × 10-17); TP53 mutations were absent in carcinomatous elements in nonhypermutated tumors and rare in previously studied ccRCCs. Mutations in known cancer drivers ATrich interaction domain 1A (ARID1A) and BRCA1 associated protein 1 (BAP1) were significantly mutated in sarcomatoid elements and were mutually exclusive with TP53 and each other. These findings provide evidence that sarcomatoid elements arise from dedifferentiation of carcinomatous ccRCCs and implicate specific genes in this process. These findings have implications for the treatment of patients with these poor-prognosis cancers. [ABSTRACT FROM AUTHOR]