Carcinoma of the collecting ducts of Bellini and renal medullary carcinoma are rare aggressive neoplasms of putative distal nephron origin. First described in 1949, case reports and review articles constitute a major source of information on collecting duct carcinoma, whereas Davis and colleagues and the pediatric tumor registry have contributed the seminal works on renal medullary carcinoma. Here we present a detailed study of collecting duct carcinoma (n=39) and renal medullary carcinoma (n=13), characterizing these rare neoplasms and analyzing their interrelationship. Both collecting duct carcinoma and renal medullary carcinoma exhibited significant similarities, such as predilection for the right kidney, tumor mass with an epicenter in the renal medulla, and a mean size of 7 cm. Overall, both tumors exhibited a poorly differentiated adenocarcinoma histology with desmoplastic stromal response (100%), inflammatory infiltrate (100%), frequent perinephric extension (collecting duct carcinoma: 97%; renal medullary carcinoma: 83%), lymphovascular invasion (100%), intraluminal mucin (collecting duct carcinoma: 42%; renal medullary carcinoma: 73%), high nuclear grade (97%), overlapping immunoreactivity for Ulex europaeus agglutinin 1 (collecting duct carcinoma: 75%; renal medullary carcinoma:55%), CK7 (collecting duct carcinoma: 44%; renal medullary carcinoma: 71%), and high-molecular weight cytokeratin (collecting duct carcinoma: 26%; renal medullary carcinoma: 29%), and nonimmunoreactivity for Ksp-cadherin. Histologically, collecting duct carcinoma frequently had tubular, tubulopapillary, or irregular glandular architecture, whereas renal medullary carcinoma commonly demonstrated islands of anastomosing tubules and cords forming irregular microcystic spaces. Multiple metastases to the lymph nodes, lung, bone, and liver were observed in both categories at presentation (collecting duct carcinoma: 17%; renal medullary carcinoma: 36%). Only patients with organ-confined small tumors were disease free beyond the median survival time. Differential clinical features between collecting duct carcinoma and renal medullary carcinoma included proclivity for younger male individuals of African ancestry with hemoglobin abnormalities and a shorter median survival of 17 weeks (vs. 44 wk for collecting duct carcinoma) for renal medullary carcinoma. The markedly overlapping clinical features, histology, immunophenotype, metastasis patterns, and uniformly aggressive outcome in collecting duct and renal medullary carcinomas suggest that renal medullary carcinoma is a distinctive clinicopathologic subtype within the entity of collecting duct carcinoma. The extremely poor prognosis and ongoing clinical trials with specific therapeutic protocols argue for their accurate distinction from other renal cell carcinoma subtypes.

Alveolar soft-part sarcoma (ASPS) is a rare, clinically, morphologically, ultrastructurally, and cytogenetically distinctive malignant mesenchymal tumor that most classically occurs in the extremities of adolescents and young adults, but has also been described in a number of unusual sites. The molecular signature of ASPS is a specific der(17)t(X;17)(p11.2;q25) translocation, which results in the fusion of TFE3 transcription factor gene (from Xp11) with ASPL at 17q25. The ASPL-TFE3 fusion protein encoded by the fusion transcript can be detected immunohistochemically with commercially available antibodies to the carboxy terminus of TFE3. Herein, we report a unique case of ASPS presenting in the bladder with subsequent urethral recurrence in a 25-year-old woman. We emphasize the differential diagnoses engendered by ASPS including common, not-so-common, and rare tumors involving the urinary bladder that have a nested architecture, and both clear and eosinophilic cytoplasm, and demonstrate the utility of a broad immunohistochemistry panel including TFE3 for diagnosis.

Chondroblastoma is a benign bone neoplasm, which usually presents in the epiphysis of long bones, but can occur in unusual locations. This report describes the clinical, radiologic, and cytologic features on FNA of two chondroblastomas of the temporomandibular region that were only recognized by histopathologic study. This emphasizes the diagnostic pitfalls of this entity and expands the cytologic differential diagnosis of tumors of the parotid region.

Overexpression of tumor-associated RAC1b has been recently highlighted as one of the most promising targets for therapeutic intervention in colon, breast, lung and pancreatic cancer. RAC1b is a hyperactive variant of the small GTPase RAC1 and has been recently shown to be overexpressed in a subset of papillary thyroid carcinomas associated with unfavorable outcome. Using the K1 PTC derived cell line as an in vitro model, we observed that both RAC1 and RAC1b were able to induce a significant increase on NF-kB and cyclin D1 reporter activity. A clear p65 nuclear localization was found in cells transfected with RAC1b-WT, confirming NF-kB canonical pathway activation. Consistently, we observed a RAC1b-mediated decrease in IκBα (NF-kB inhibitor) protein levels. Moreover, we show that RAC1b overexpression stimulates G1/S progression and protects thyroid cells against induced apoptosis, the latter through a process involving the NF-kB pathway. Present data support previous findings suggesting an important role for RAC1b in the development of follicular cell-derived thyroid malignancies and point out NF-kB activation as one of the molecular mechanisms associated with the pro-tumorigenic advantage of RAC1b overexpression in thyroid carcinomas.

The results of this study suggest that TERT promoter and EIF1AX mutations are not frequently involved in FNMTC aetiology. However, we show for the first time that TERT alterations are associated with familial thyroid tumour progression. Our data also suggest that TERT mutations are more often found in concomitance with BRAF mutations in advanced stages of FNMTC.