Popliteal artery entrapment syndrome treated by a posterior approach in a 15-year-old athlete.

Popliteal artery entrapment syndrome is a rare source of claudication in young people. We present the case of a 15-year-old male athlete who presented with intermittent numbness of his right foot with exertion. Imaging revealed classic compression from a right type III popliteal artery entrapment. The left popliteal artery was chronically occluded with a large collateral vessel. He underwent release of the accessory bands of the gastrocnemius muscle with significant arteriolysis on the right side via a posterior approach. Chronic popliteal artery entrapment can be treated from a posterior approach, resulting in arterial occlusion and will be asymptomatic if well collateralized.

Low saliva pH can yield false positives results in simple RT-LAMP-based SARS-CoV-2 diagnostic tests.

Diagnosis of any infectious disease is vital for opportune treatment and to prevent dissemination. RT-qPCR tests for detection of SARS-CoV-2, the causative agent for COVID-19, are ideal in a hospital environment. However, mass testing requires cheaper and simpler tests, especially in settings that lack sophisticated machinery. The most common current diagnostic method is based on nasopharyngeal sample collection, RNA extraction, and RT-qPCR for amplification and detection of viral nucleic acids. Here, we show that samples obtained from nasopharyngeal swabs in VTM and in saliva can be used with or without RNA purification in an isothermal loop-mediated amplification (LAMP)-based assay, with 60-93% sensitivity for SARS-CoV-2 detection as compared to standard RT-qPCR tests. A series of simple modifications to standard RT-LAMP published methods to stabilize pH fluctuations due to salivary acidity resulted in a significant improvement in reliability, opening new avenues for efficient, low-cost testing of COVID-19 infection.

Genomic and immunohistochemical analysis in human adrenal cortical neoplasia reveal beta-catenin mutations as potential prognostic biomarker.

Evaluation for malignancy of the adrenal cortex, adrenal cortical carcinoma (ACC), is a challenge in surgical pathology due to its relative rarity and histologic overlap with its benign counterpart, adrenocortical adenoma (ACA). We characterized a cohort of human ACC and ACA, including a molecular screen, with a goal of identifying potential diagnostic adjuncts. Thirty-six cases of ACC underwent histologic and clinical review. In the 31 ACC cases with available material and a cohort of 10 ACA cases, a multiplex nucleotide amplification molecular screen from formalin-fixed, paraffin-embedded tissue was peformed. ACCs demonstrated a wide variety of clinical and histologic characteristics with overall poor but unpredictable survival for subjects with ACC. By mutational screen, 12/31 (38.7%) carcinomas harbored CTNNB1 mutations, 1 with an additional TP53 mutation; 1 case each had isolated APC and TP53 mutations; 16 were wild-type for all tested loci; and 1 case demonstrated repeated assay failures. Two of the 10 ACA (20%) demonstrated CTNNB1 mutations by mutational screen, with no additional mutations. Immunohistochemistry for beta-catenin was performed and compared with the results of the molecular screen. Strong nuclear beta-catenin immunopositivity corresponded to the presence of CTNNB1 mutation by genotyping in 10 of 12 cases (83% sensitivity); the mismatched case(s) demonstrated strong membranous staining by immunohistochemistry. Seventeen of the 18 cases without CTNNB1 mutation showed membranous staining or did not stain (94% specificity); the mismatched case demonstrated scattered (<10%) positive nuclei. Both mutations in ACA were corroborated with immunohistochemistry for beta-catenin. No histomorphologic parameter appeared dominant in lesions with a particular mutational status. Based on these results, mutational status of CTNNB1 in adrenal cortical neoplasms can be predicted with reasonable accuracy by immunohistochemical cellular localization. Nuclear localization of beta-catenin by immunostain may be helpful in analysis of select lesions of the adrenal cortex whose biological behavior is uncertain from clinical and histologic information; a larger cohort is required to test this hypothesis.

Diagnosis and successful surgical management of posterior nutcracker syndrome in a patient with loin pain hematuria.

The syndrome of loin pain hematuria in the absence of stones is poorly understood but must be considered in the differential diagnosis for patients with clinical manifestations resembling nephrolithiasis. A 22-year-old white female with a 4-year history of left flank pain and hematuria underwent an extensive workup with normal renal ultrasound and cystourethroscopies. CT scan and MRI revealed a retro-aortic left renal vein. Posterior nutcracker syndrome was considered the most likely diagnosis. The patient underwent a left laparoscopic nephrectomy with auto-transplantation in the right iliac fossa. She developed azotemia shortly after, which resolved and since then has become asymptomatic.

Activation of PI3K signaling in Merkel cell carcinoma.

PURPOSE: Merkel cell carcinoma (MCC) is an aggressive cutaneous neuroendocrine tumor, often metastatic at presentation, for which current chemotherapeutic regimens are largely ineffective. As its pathogenesis is still unknown, we hypothesized that deregulation of signaling pathways commonly activated in cancer may contribute to MCC tumorigenesis and may provide insights into targeted therapy approaches for this malignancy. EXPERIMENTAL DESIGN: We retrospectively profiled 60 primary MCC samples using a SNaPshot-based tumor genotyping assay to screen for common mutations in 13 cancer genes. RESULTS: We identified mutations in 9 (15%) MCC primary tumors, including mutations in TP53 (3 of 60) and activating mutations in the PIK3CA gene (6 of 60). Sanger sequencing of the primary MCC tumors detected one additional PIK3CA mutation (R19K) that had not been previously described in cancer. Merkel cell polyoma virus (MCPyV) was detected in 38 (66%) MCC cases and patients with MCPyV-positive cancers showed a trend toward better survival. With one exception, the presence of MCPyV and activating mutations in PIK3CA appeared mutually exclusive. We observed that signaling through the PI3K/pAKT pathway was active in one MCPyV-positive and in all MCPyV-negative MCC cell lines, as evidenced by AKT phosphorylation. Importantly, the presence of a PIK3CA-activating mutation was associated with sensitivity to treatment with ZST474, a specific phosphoinositide 3-kinase (PI3K) inhibitor, and to NVP-BEZ235, a dual PI3K/mTOR inhibitor, targeted agents under active clinical development. CONCLUSIONS: PI3K pathway activation may drive tumorigenesis in a subset of MCC and screening these tumors for PIK3CA mutations could help identify patients who may respond to treatment with PI3K pathway inhibitors.

Malignant neurocristic hamartoma: a tumor distinct from conventional melanoma and malignant blue nevus.

Neurocristic hamartomas are rare pigmented lesions comprised of melanocytes, Schwann cells, and pigmented dendritic spindle cells that involve the skin and soft tissue. Malignant transformation can rarely arise within neurocristic hamartomas. Up to date, there has been only 1 series of 7 cases of malignant neurocristic hamartomas (MNHs), with 3 cases that developed metastases. We present the histology and clinical course of 3 additional cases of MNH, 2 of which were metastatic. CD117 was strongly positive in all cases with available archival materials--the tumors and background neurocristic hamartoma of 3 cases, and 1 lymph node metastasis; however, KIT sequencing for exons 11, 13, 17, and 18 was negative. Mutational analyses of recurrent mutations of 17 cancer genes, including BRAF and KIT, were also negative. Although our series is small, KIT overexpression in MNH does not seem to correlate with gene mutation. The lack of BRAF, NRAS, GNAQ, and KIT mutations seems to support the notion that MNH may be distinct from conventional melanoma and from other dermal melanomas, such as malignant blue nevi and melanoma arising in congenital nevi.

BRAF V600E mutations are common in pleomorphic xanthoastrocytoma: diagnostic and therapeutic implications.

Pleomorphic xanthoastrocytoma (PXA) is low-grade glial neoplasm principally affecting children and young adults. Approximately 40% of PXA are reported to recur within 10 years of primary resection. Upon recurrence, patients receive radiation therapy and conventional chemotherapeutics designed for high-grade gliomas. Genetic changes that can be targeted by selective therapeutics have not been extensively evaluated in PXA and ancillary diagnostic tests to help discriminate PXA from other pleomorphic and often more aggressive astrocytic malignancies are limited. In this study, we apply the SNaPshot multiplexed targeted sequencing platform in the analysis of brain tumors to interrogate 60 genetic loci that are frequently mutated in 15 cancer genes. In our analysis we detect BRAF V600E mutations in 12 of 20 (60%) WHO grade II PXA, in 1 of 6 (17%) PXA with anaplasia and in 1 glioblastoma arising in a PXA. Phospho-ERK was detected in all tumors independent of the BRAF mutation status. BRAF duplication was not detected in any of the PXA cases. BRAF V600E mutations were identified in only 2 of 71 (2.8%) glioblastoma (GBM) analyzed, including 1 of 9 (11.1%) giant cell GBM (gcGBM). The finding that BRAF V600E mutations are common in the majority of PXA has important therapeutic implications and may help in differentiating less aggressive PXAs from lethal gcGBMs and GBMs.

A potential role for targeted therapy in a subset of metastasizing adnexal carcinomas.

Metastasizing adnexal carcinomas are rare; thus, currently there is no uniform treatment guideline. Chemotherapeutic drugs that selectively target cancer-promoting pathways may complement conventional therapeutic approaches. We performed immunohistochemistry (epidermal growth factor receptor (EGFR), HER2, and CD117), EGFR and ERBB2 fluorescence in situ hybridization (FISH), and multiplexed SNaPshot® genotyping (testing for recurrent mutations in 15 cancer genes including BRAF, EGFR, KRAS, PIK3CA, and TP53) on primary tumors and corresponding metastases of 14 metastasizing adnexal carcinomas (three apocrine, six eccrine, two hidradenocarcinomas, two porocarcinomas, and one aggressive digital papillary adenocarcinoma). Metastasis to regional lymph node was most common, followed by skin and then lungs. Follow-up was available in 12 patients (5 months to 8 years) with 1 died of widespread metastases. Although EGFR overexpression was a prevalent feature in this cohort, seen in 7/11 (64%) primary tumors and 10/14 (71%) metastases; FISH for EGFR gene amplification was negative in 9 tested primary tumors and 12 metastases. FISH of the one primary tumor and three metastases with 2+ HER2 overexpression revealed a low level of ERBB2 gene amplification in one apocrine carcinoma and corresponding metastasis. CD117 expression was seen only in rare cases. PIK3CA (2/12, 17%) and TP53 (3/12, 25%) mutations were detected in two (one hidradenocarcinoma, one porocarcinoma) and three (one eccrine, one hidradenocarcinoma, and one aggressive digital papillary adenocarcinoma) cases, respectively. The role of EGFR inhibitor therapy in metastasizing adnexal carcinomas with protein overexpression remains unclear. Targeted therapy including PI3K pathway inhibitors might be a potential treatment for rare cases of adnexal carcinomas with metastases.

Acute schistosomiasis in nonimmune travelers: chest CT findings in 10 patients.

OBJECTIVE: We describe the findings of unenhanced chest CT in 10 patients with acute schistosomiasis. CONCLUSION: Despite the absence of pulmonary symptoms in four individuals, all patients had parenchymal abnormalities. Small pulmonary nodules were the most common finding, identified in nine patients. These nodules ranged in size from 2 to 5 mm in five patients, with larger nodules ranging up to 15 mm seen in four patients. In one patient, the only parenchymal abnormality was a single 5-mm focus of ground-glass attenuation. No relationship was seen between either the presence of pulmonary symptoms or the presence of peripheral eosinophilia and the severity of parenchymal disease. No additional significant findings were identified.