Urothelial carcinoma in situ (CIS) is a high-grade noninvasive malignancy with a high tendency of progression. Although it is typically grouped with other nonmuscle invasive bladder cancers, its higher grade and aggressiveness make it a unique clinical entity. Urothelial CIS is histologically characterized by replacement of the urothelium by cells which fulfill the morphologic criteria of malignancy including nuclear pleomorphism, hyperchromasia, prominent nucleoli, and increased numbers of normal and abnormal mitoses. Urothelial CIS may be categorized as primary when it is not associated with any past or present urothelial carcinoma. It is termed as secondary when there is concomitant or previous urothelial carcinoma in the patient. In recent years detailed molecular studies have provided valuable data for intrinsic molecular subclassification of urothelial carcinoma into 2 broad categories namely luminal and basal types with significant implications for prognosis and therapy. Similar studies on urothelial CIS are limited but have provided crucial insight into the molecular basis of CIS. These studies have revealed that urothelial CIS may also be divided into luminal and basal subtypes, but luminal subtype is much more common. It has also been shown that in many cases, luminal type of urothelial CIS may undergo a class switch to basal type during progression to an invasive carcinoma. Additional studies may be required to confirm and further elaborate these findings.
Cytokeratins belong to the family of intermediate filaments. They are expressed in a highly specific manner in epithelial cells where they play a crucial role in the integrity and mechanical stability of the cells. Several types of cytokeratins have been described in normal as well as neoplastic urothelium. In the case of urothelial neoplasms expression of CK20 and CK5/6 has been shown in several studies to have diagnostic and prognostic implications. Thus, low-grade urothelial carcinoma manifests CK expression limited to the umbrella cells, while high-grade tumors usually have an expression in the entire thickness of the urothelium except for the basal layer. CK5/6 expression on the other hand is expressed in the basal cells in all low-grade and some high-grade urothelial carcinomas. Diffuse CK20 staining accompanied by loss of CK5/6-positive basal layer is usually associated with aggressive clinical behavior. Double staining of the slides for these cytokeratins may facilitate proper interpretation and correlation.
Background The pure large cell type is a rare variant of primary neuroendocrine carcinoma of the gallbladder. Few reports have mentioned extended survival. Although a multimodal treatment has been described in the treatment of such rare disease, redo liver resection has not yet been mentioned. Case report A 67-year-old lady was found to have poorly differentiated, high grade, pure large cell neuroendocrine tumor of the gallbladder after cholecystectomy for gallstones. After the diagnosis, staging workup showed a lesion in segment IVB/V of the liver, and chromogranin was elevated (982 mcg/L). The patient underwent central inferior hepatectomy and wedge excision of a lesion in segment III (discovered intra-operatively), with hilar lymphadenectomy. Three months after the first liver resection, she developed a new liver lesion II/III and underwent left lateral liver resection. The patient remained disease-free for 4 months following the second liver resection but then developed recurrent liver disease and was started on chemotherapy. Further progression led to multi-organ failure and death at 26 months from initial diagnosis. Conclusion This is the first reported repeat liver resection in such a rare disease that has led to extended overall survival. We suggest that a group of selected patients with this rare malignancy, and liver-limited disease, may benefit from repeated liver resection.
Bladder cancer is a highly prevalent disease throughout the world usually encountered in older patients, and associated with substantial morbidity, mortality, and cost. The treatment of bladder cancer has remained unchanged for the last several decades. However, in recent years the availability of comprehensive genomic data from The Cancer Genome Atlas and other large projects have considerably improved our understanding of the pathogenesis of these tumors. These studies demonstrated that bladder cancers can be grouped into 2 broad categories namely basal and luminal molecular subtypes with recognizable subgroups in each of these categories. Clinical data suggest that invasive basal cancers are more sensitive to neoadjuvant chemotherapy (NAC), such that most patients with basal cancers who are aggressively managed with NAC have excellent outcomes. Patients with luminal cancers do not appear to derive much clinical benefit from NAC, but some may appear to be sensitive to anti-programmed death-ligand 1 (PDL1) antibodies and possibly other immune checkpoint inhibitors. It is hoped that future studies will also identify biomarkers such as immunohistochemical markers which may be used to predict therapeutic response of these tumors. This will contribute substantially toward efficient and cost-effective diagnosis and management of these neoplasms.
A well-marginated fat-containing renal lesion gives strong suspicion of renal angiomyolipoma (RAML) that usually requires no surgical intervention. Radiologically, renal masses with a large amount of fat can rule out renal cell carcinoma (RCC). Calcifications are very infrequent in RAML. However, the presence of calcifications in a fat-containing renal lesion is highly suggestive of RCC. These lesions should undergo surgical resection and histopathological assessment to reach the right diagnosis and avoid poor outcomes if diagnosed late. We present a case of bilateral renal tumors, in which one of them radiologically contained abundant fat with calcifications on CT scan, which was confirmed to be an RCC on histopathological examination.
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