Aline C. Tregnago

Orbital melanocytoma completely resected with conservative surgery in association with ipsilateral nevus of Ota: Report of a case and review of the literature

Melanocytomas are rare pigmented primary lesions of the central nervous system arising from melanocytes of leptomeninges. They occur most frequently in the posterior fossa, Meckels cave, or along the cervical and thoracic spinal cord. Orbital melanocytomas have been rarely reported. Nevus of Ota is a melanocytic lesion that can be associated with cutaneous and meningeal melanocytic neoplasms.

GATA3 expression in primary vulvar Paget disease: a potential pitfall leading to misdiagnosis of pagetoid urothelial intraepithelial neoplasia

GATA3 has been reported as a specific urothelial marker among organs in the pelvic region, and has been classified as highly sensitive and specific for urothelial and breast carcinomas. Our aim was to verify GATA3 expression in extramammary Paget disease, and to determine whether it can be use to differentiate primary vulvar Paget disease from pagetoid urothelial intraepithelial neoplasia (PUIN). We also analysed HER2 protein expression and HER2 gene amplification and their roles as prognostic factors in extramammary Paget disease.

Non-invasive detection of urothelial cancer through the analysis of driver gene mutations and aneuploidy

Current non-invasive approaches for detection of urothelial cancers are suboptimal. We developed a test to detect urothelial neoplasms using DNA recovered from cells shed into urine. UroSEEK incorporates massive parallel sequencing assays for mutations in 11 genes and copy number changes on 39 chromosome arms. In 570 patients at risk for bladder cancer (BC), UroSEEK was positive in 83% of those who developed BC. Combined with cytology, UroSEEK detected 95% of patients who developed BC. Of 56 patients with upper tract urothelial cancer, 75% tested positive by UroSEEK, including 79% of those with non-invasive tumors. UroSEEK detected genetic abnormalities in 68% of urines obtained from BC patients under surveillance who demonstrated clinical evidence of recurrence. The advantages of UroSEEK over cytology were evident in low-grade BCs; UroSEEK detected 67% of cases whereas cytology detected none. These results establish the foundation for a new non-invasive approach for detection of urothelial cancer.

Insulin-like growth factor-1 receptor expression in upper tract urothelial carcinoma

Insulin-like growth factor-1 receptor (IGF1R) is a transmembrane tyrosine kinase receptor that plays a crucial role in cell proliferation, growth, differentiation, and apoptosis. IGF1R overexpression has been observed in several cancers, including invasive bladder carcinomas, as a potential prognostic factor. Given known biologic differences between upper and lower urinary tract urothelial carcinoma, we assessed the expression status and prognostic significance of IGF1R in upper tract urothelial carcinoma (UTUC). Two tissue microarrays (TMAs) were built from 99 Japanese patients with non-metastatic UTUC submitted to radical nephroureterectomy between 1997 and 2011. TMAs were constructed with triplicate tumor and paired benign urothelium. Membranous IGF1R staining was evaluated using immunohistochemistry. Two scoring methods were applied (Her2-score and H-score). The highest score was assigned to each tumor. IGF1R positivity was defined as Her2-score ≥ 1+. Association with clinicopathologic parameters and outcome was assessed using hazard ratios (HR) with 95% confidence intervals (CI) and adjusted P values. We found positive IGF1R expression in 70% of UTUC. Outcomes were as follows: tumor recurrence, 33%; tumor progression, 59%; overall mortality, 33%; and cancer-specific mortality, 30%. IGF1R was not associated with any clinicopathologic features. In addition, IGF1R expression was not associated with tumor recurrence (HR = 0.54, CI = 0.25–1.1, P = 0.11), tumor progression (HR = 1.6, CI = 0.8–3.1, P = 0.19), overall mortality (HR = 1.5, CI = 0.68–3.4, P = 0.31), or cancer-specific mortality (HR = 1.6, CI = 0.68–3.8, P = 0.27). Positive IGF1R expression was found in more than two thirds of UTUC. This finding provides a rationale to investigate IGF1R as a potential therapeutic target in UTUC. In contrast to bladder cancer, IGF1R expression in UTUC did not correlate with outcome, further pointing to biologic differences between UTUC and bladder cancer.

MP65-14 UROSEEK: A NOVEL NON-INVASIVE MOLECULAR ASSAY FOR SURVEILLANCE OF BLADDER CANCER

Simeon Springer, Baltimore, MD; Maria Del Carmen Rodriguez Pena*, Birmingham, AL; Aline Tregnago, Baltimore, MD; Diana Taheri, Tehran, Islamic Republic of Iran; Stephania Bezerra, Isabela Cunha, S~ ao Paulo, Brazil; Kazutoshi Fujita, Osaka, Japan; Dilek Baydar, Hacettepe, Turkey; Trinity Bivalacqua, Nickolas Papadopoulos, Kenneth W Kinzler, Bert Vogelstein, Baltimore, MD; George Netto, Birmingham, AL

Inflammatory pseudotumor-like follicular dendritic cell tumor: an underdiagnosed neoplasia

Follicular dendritic cell (FDC) tumor is an uncommon neoplasm. It generally presents as a slow-growing, painless mass, without systemic symptoms. Histological features usually include low grade spindle cell proliferation. This tumor occurs primarily in lymph nodes, especially cervical and axillary, however, involvement of extranodal sites such as the tonsils, spleen, liver, and gastrointestinal tract has been reported. Inflammatory pseudotumor-like follicular dendritic cell tumor (IPT-like FDCT) is a rare, distinctive histological subtype of this low-grade malignant neoplasm, with consistent Epstein-Barr virus (EBV) association. The differential diagnosis with other fibro-inflammatory tumor proliferations, as inflammatory pseudotumor (IPT) and inflammatory myofibroblastic tumor (IMT), may be challenging. In the present article, two cases of IPT-like FDCT of the spleen are presented, with a broad overview of the literature: one 77-year-old male and one 70-year-old female. A large immunohistochemical panel should be used for diagnosis, as no single specific and totally sensitive markers are available, including markers for CD21, CD23, CD35, CNA42, and clusterin. Individual cases may express one or more of these markers, so that all of them should be investigated. In situ hybridization for EBV is constantly positive. Immunostaining for ALK should be negative, as it is present in roughly half of the cases of IMT. This panel should be used in combination of clinical, laboratory, and topographic evidences. Importantly, inclusion of this lesion as a possible option in clinical and pathological investigation represents the basis for a correct diagnosis.

Osteogenic Melanoma with Desmin Expression

Background: Osteogenic differentiation is rarely seen in melanomas, when it occurs it is mainly in acral lesions. Methods: We report a case of an osteogenic melanoma in a 49-year-old woman who presented with a pigmented lesion in the subungueal region of her left hallux. The lesion was ulcerated and infiltrated until the deep dermis without bone involvement. Results: The tumor was composed of pleomorphic atypical epithelioid and fusiform cells disposed in nests or cords, with vesicular nuclei and prominent central nucleoli. Focal lentiginous proliferation of large atypical melanocytes was present along the dermoepidermal junction. Areas of osteoid matrix focally mineralized were disposed in trabeculae, and there were islands of neoplastic cells. Immunohistochemistry revealed strong expression of S-100 protein and, unexpectedly, of desmin. Focal expression of Melan-A, microphthalmia transcription factor, and HMB-45 is also revealed. Mutations in BRAF and NRAS genes were not present. The patient was submitted to an amputation of the left hallux with negative sentinel lymph node. Conclusion: The importance of recognizing osteogenic melanoma is based on difficulties for histologic recognition and its differentials diagnosis.