Images
Clear-cell renal-cell carcinoma. Macroscopy
Clear-cell renal-cell carcinoma. HE, × 100
Clear-cell renal-cell carcinoma. Fuhrman grade = 1. HE, × 400
Grade 3: Arrows point at a clearly visible nucleolus.
Clear-cell renal-cell carcinoma (CCRCC) is a type of renal-cell carcinoma.
Several frequently mutated genes were discovered in CCRCC: VHL, KDM6A/UTX, SETD2, KDM5C/JARID1C and MLL2. PBRM1 is also commonly mutated in CCRCC.[ citation needed ]
CCRCC is derived from the proximal convoluted tubule.[ citation needed ]
Generally, the cells have a clear cytoplasm, are surrounded by a distinct cell membrane and contain round and uniform nuclei.[ citation needed ]
Microscopically, CCRCCs are graded by the ISUP/WHO as follows: [1] [2]
Von Hippel–Lindau disease (VHL), also known as VonHippel–Lindau syndrome, is a rare genetic disorder with multisystem involvement. It is characterized by visceral cysts and benign tumors with potential for subsequent malignant transformation. It is a type of phakomatosis that results from a mutation in the Von Hippel–Lindau tumor suppressor gene on chromosome 3p25.3.
Renal cell carcinoma (RCC) is a kidney cancer that originates in the lining of the proximal convoluted tubule, a part of the very small tubes in the kidney that transport primary urine. RCC is the most common type of kidney cancer in adults, responsible for approximately 90–95% of cases. RCC occurrence shows a male predominance over women with a ratio of 1.5:1. RCC most commonly occurs between 6th and 7th decade of life.
Polycythemia is a laboratory finding in which the hematocrit and/or hemoglobin concentration are increased in the blood. Polycythemia is sometimes called erythrocytosis, and there is significant overlap in the two findings, but the terms are not the same: polycythemia describes any increase in hematocrit and/or hemoglobin, while erythrocytosis describes an increase specifically in the number of red blood cells in the blood.
Birt–Hogg–Dubé syndrome (BHD), also Hornstein–Birt–Hogg–Dubé syndrome, Hornstein–Knickenberg syndrome, and fibrofolliculomas with trichodiscomas and acrochordons is a human autosomal dominant genetic disorder that can cause susceptibility to kidney cancer, renal and pulmonary cysts, and noncancerous tumors of the hair follicles, called fibrofolliculomas. The symptoms seen in each family are unique, and can include any combination of the three symptoms. Fibrofolliculomas are the most common manifestation, found on the face and upper trunk in over 80% of people with BHD over the age of 40. Pulmonary cysts are equally common (84%), but only 24% of people with BHD eventually experience a collapsed lung. Kidney tumors, both cancerous and benign, occur in 14–34% of people with BHD; the associated kidney cancers are often rare hybrid tumors.
Prefoldin subunit 3 (VBP-1), also Von Hippel–Lindau binding protein 1, is a prefoldin chaperone protein that binds to von Hippel–Lindau protein and transports it from perinuclear granules to the nucleus or cytoplasm inside the cell. It is also involved in transporting nascent polypeptides to cytosolic chaperonins for post-translational folding.
Phakomatoses, also known neurocutaneous syndromes, are a group of multisystemic diseases that most prominently affect structures primarily derived from the ectoderm such as the central nervous system, skin and eyes. The majority of phakomatoses are single-gene disorders that may be inherited in an autosomal dominant, autosomal recessive or X-linked pattern. Presentations may vary dramatically between patients with the same particular syndrome due to mosaicism, variable expressivity, and penetrance.
Hemangioblastomas, or haemangioblastomas, are vascular tumors of the central nervous system that originate from the vascular system, usually during middle age. Sometimes, these tumors occur in other sites such as the spinal cord and retina. They may be associated with other diseases such as polycythemia, pancreatic cysts and Von Hippel–Lindau syndrome. Hemangioblastomas are most commonly composed of stromal cells in small blood vessels and usually occur in the cerebellum, brainstem or spinal cord. They are classed as grade I tumors under the World Health Organization's classification system.
The Von Hippel–Lindau tumor suppressor also known as pVHL is a protein that, in humans, is encoded by the VHL gene. Mutations of the VHL gene are associated with Von Hippel–Lindau disease.
Congenital mesoblastic nephroma, while rare, is the most common kidney neoplasm diagnosed in the first three months of life and accounts for 3-5% of all childhood renal neoplasms. This neoplasm is generally non-aggressive and amenable to surgical removal. However, a readily identifiable subset of these kidney tumors has a more malignant potential and is capable of causing life-threatening metastases. Congenital mesoblastic nephroma was first named as such in 1967 but was recognized decades before this as fetal renal hamartoma or leiomyomatous renal hamartoma.
JADE1 is a protein that in humans is encoded by the JADE1 gene.
Ubiquitin carboxyl-terminal hydrolase 20 is an enzyme that in humans is encoded by the USP20 gene.
BRICK1 is a putative micropeptide protein that in humans is encoded by the C3orf10 gene.
Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare subtype of renal cell carcinoma (RCC), that is included in the 2004 WHO classification of RCC. MTSCC is a rare neoplasm and is considered as a low-grade entity. It may be a variant of papillary RCC. This tumor occurs throughout life and is more frequent in females.
Clear cell papillary renal cell carcinoma (CCPRCC) is a rare subtype of renal cell carcinoma (RCC) that has microscopic morphologic features of papillary renal cell carcinoma and clear cell renal cell carcinoma, yet is pathologically distinct based on molecular changes and immunohistochemistry.
An endolymphatic sac tumor (ELST) is a very uncommon papillary epithelial neoplasm arising within the endolymphatic sac or endolymphatic duct. This tumor shows a very high association with Von Hippel–Lindau syndrome (VHL).
Hereditary leiomyomatosis and renal cell carcinoma (HLRCC) or Reed's syndrome is rare autosomal dominant disorder associated with benign smooth muscle tumors and an increased risk of renal cell carcinoma. It is characterised by multiple cutaneous leiomyomas and, in women, uterine leiomyomas. It predisposes for renal cell cancer, an association denominated hereditary leiomyomatosis and renal cell cancer, and it is also associated with increased risk of uterine leiomyosarcoma. The syndrome is caused by a mutation in the fumarate hydratase gene, which leads to an accumulation of fumarate. The inheritance pattern is autosomal dominant.
A cancer syndrome, or family cancer syndrome, is a genetic disorder in which inherited genetic mutations in one or more genes predispose the affected individuals to the development of cancers and may also cause the early onset of these cancers. Cancer syndromes often show not only a high lifetime risk of developing cancer, but also the development of multiple independent primary tumors.
William G. Kaelin Jr. is an American Nobel Laureate physician-scientist. He is a professor of medicine at Harvard University and the Dana–Farber Cancer Institute. His laboratory studies tumor suppressor proteins. In 2016, Kaelin received the Albert Lasker Award for Basic Medical Research and the AACR Princess Takamatsu Award. He also won the Nobel Prize in Physiology or Medicine in 2019 along with Peter J. Ratcliffe and Gregg L. Semenza.
Papillary renal cell carcinoma (PRCC) is a malignant, heterogeneous tumor originating from renal tubular epithelial cells of the kidney, which comprises approximately 10-15% of all kidney neoplasms. Based on its morphological features, PRCC can be classified into two main subtypes, which are type 1 (basophilic) and type 2 (eosinophilic).
Belzutifan, sold under the brand name Welireg, is a medication used for the treatment of von Hippel–Lindau disease-associated renal cell carcinoma. It is taken by mouth.