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Kidney Cancer: Pathology: Difference between revisions

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|'''<span style="color:#0000ff">HIPPPEEL</span>'''
|'''<span style="color:#0000ff">HIPPPEEL</span>'''


# '''<span style="color:#ff0000">CNS and/or retinal </span><span style="color:#0000ff">H</span>emangioblastomas</span>'''
# '''<span style="color:#ff0000">CNS and/or retinal </span><span style="color:#0000ff">H</span><span style="color:#ff0000">emangioblastomas</span>'''
# '''<span style="color:#ff0000">ccRCC (</span><span style="color:#0000ff">I</span><span style="color:#ff0000">ncreased risk) and renal cysts</span>'''
# '''<span style="color:#ff0000">ccRCC (</span><span style="color:#0000ff">I</span><span style="color:#ff0000">ncreased risk) and renal cysts</span>'''
# '''<span style="color:#0000ff">P</span><span style="color:#ff0000">heochromocytoma</span>'''
# '''<span style="color:#0000ff">P</span><span style="color:#ff0000">heochromocytoma</span>'''
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# '''<span style="color:#ff0000">Broad </span><span style="color:#0000ff">L</span><span style="color:#ff0000">igament tumours</span>'''
# '''<span style="color:#ff0000">Broad </span><span style="color:#0000ff">L</span><span style="color:#ff0000">igament tumours</span>'''
|-
|-
|'''Hereditary Papillary Renal Carcinoma (HPRCC)'''
|'''<span style="color:#ff0000">Hereditary Papillary Renal Carcinoma (HPRCC)</span>'''
|'''''c-MET'''''
|'''''<span style="color:#ff0000">c-MET</span>'''''
|
|
# '''Type 1 papillary RCC'''
# '''<span style="color:#ff0000">Type 1 papillary RCC</span>'''
|-
|-
|'''Hereditary Leiomyomatosis and RCC (HLRCC)*'''
|'''<span style="color:#ff0000">Hereditary Leiomyomatosis and RCC (HLRCC)*</span>'''
|'''Fumarate hydratase'''
|'''<span style="color:#ff0000">Fumarate hydratase</span>'''
|
|
# '''Type 2 papillary or collecting duct RCC'''
# '''<span style="color:#ff0000">Type 2 papillary or collecting duct RCC</span>'''
# '''Cutaneous leioyomyomas'''
# '''<span style="color:#ff0000">Cutaneous leioyomyomas</span>'''
 
# '''<span style="color:#ff0000">Uterine leiyomyomas</span>'''
# '''Uterine leiyomyomas'''
|-
|-
|'''Birt-Hogg-Dube (BHD)'''
|'''<span style="color:#ff0000">Birt-Hogg-Dube (BHD)</span>'''
|'''Folliculin'''
|'''<span style="color:#ff0000">Folliculin</span>'''
|
|
# '''Skin fibrofolliculomas'''
# '''<span style="color:#ff0000">Skin fibrofolliculomas</span>'''
# '''Pulmonary cysts, spontaneous pneumothoraces'''
# '''<span style="color:#ff0000">Pulmonary cysts, spontaneous pneumothoraces</span>'''
# '''Variety of renal tumours (including chromophobe RCC, oncocytoma, hybrid oncocytic/chromophobe tumors, clear cell RCC (rare), renal cysts)'''
# '''<span style="color:#ff0000">Variety of renal tumours (including chromophobe RCC, oncocytoma, hybrid oncocytic/chromophobe tumors,</span> clear cell RCC (rare), renal cysts)'''
|-
|-
|'''Succinate Dehydrogenase RCC*'''
|'''<span style="color:#ff0000">Succinate Dehydrogenase RCC*</span>'''
|'''''SDHB/C/D (encoding subunits of the Krebs cycle enzyme succinate dehydrogenase)'''''
|'''''SDHB/C/D (encoding subunits of the Krebs cycle enzyme succinate dehydrogenase)'''''
|
|
# '''Variety of renal tumours (clear cell RCC, chromophobe RCC, type 2 papillary RCC, oncocytoma)'''
# '''Variety of renal tumours (clear cell RCC, chromophobe RCC, type 2 papillary RCC, oncocytoma)'''
# '''Adrenal pheochromocytoma/paraganglioma'''
# '''<span style="color:#ff0000">Adrenal pheochromocytoma/paraganglioma</span>'''
|-
|-
|'''Tuberous Sclerosis Complex (TSC)'''
|'''<span style="color:#ff0000">Tuberous Sclerosis Complex (TSC)</span>'''
|'''''TSC1/2'''''
|'''''<span style="color:#ff0000">TSC1/2</span>'''''
|
|
# '''Skin (adenoma subaceum, shagreen spots)'''
# '''<span style="color:#ff0000">Skin (adenoma subaceum, shagreen spots)</span>'''
# '''Variety of renal tumours (increased predisposition for ccRCC, AMLs, renal cysts, polycystic kidney disease, oncycytoma)'''
# '''<span style="color:#ff0000">Variety of renal tumours (increased predisposition for ccRCC, AMLs,</span> renal cysts, polycystic kidney disease, oncycytoma)'''
# '''Retinal hamartomas'''
# '''<span style="color:#ff0000">Retinal hamartomas</span>'''
# '''CNS lesions (including tubers)'''
# '''<span style="color:#ff0000">CNS lesions (including tubers)</span>'''
# '''Seizures'''
# '''<span style="color:#ff0000">Seizures</span>'''
# '''Intellectual disability'''
# '''<span style="color:#ff0000">Intellectual disability</span>'''
# '''Cardiac lesions'''
# '''<span style="color:#ff0000">Cardiac lesions</span>'''
# '''Teeth/gum lesions'''
# '''<span style="color:#ff0000">Teeth/gum lesions</span>'''
# '''Bone cysts'''
# '''<span style="color:#ff0000">Bone cysts</span>'''
# '''Pulmonary lymphangiomyomatosis'''
# '''<span style="color:#ff0000">Pulmonary lymphangiomyomatosis</span>'''
|-
|-
|'''Cowden/PTEN Syndrome Associated RCC'''  
|'''Cowden/PTEN Syndrome Associated RCC'''  
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* '''Malignancies in other organ systems (breast, thyroid)'''
* '''Malignancies in other organ systems (breast, thyroid)'''
|-
|-
|'''BAP-1 tumour predisposition syndrome'''§
|'''<span style="color:#ff0000">BAP-1 tumour predisposition syndrome</span>'''§
|'''BAP1'''
|'''<span style="color:#ff0000">BAP1</span>'''
|
|
* '''ccRCC'''
* '''<span style="color:#ff0000">ccRCC</span>'''
* '''Uveal melanoma'''
* '''<span style="color:#ff0000">Uveal melanoma</span>'''
* '''Malignant mesothelioma'''
* '''Malignant mesothelioma'''
* '''Cutaneous melanoma'''
* '''Cutaneous melanoma'''
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* '''Basal cell carcinoma'''
* '''Basal cell carcinoma'''
|-
|-
| colspan="3" |'''*Renal cancers associated with these syndromes are typically more aggressive'''
| colspan="3" |'''<span style="color:#ff0000">*Renal cancers associated with these syndromes are typically more aggressive</span>'''
|}
|}


* '''Von Hippel-Lindau Disease'''
* '''<span style="color:#ff0000">Von Hippel-Lindau Disease</span>'''
** Incidence 1:30,000-1:40,000
** Incidence 1:30,000-1:40,000
** '''RCC develops in 35-70% of VHL patients and is''' '''distinctive for early age (median 40) of onset and bilateral and multifocal involvement'''
** '''<span style="color:#ff0000">RCC develops in 35-70% of VHL patients</span> and is''' '''distinctive for early age (median 40) of onset and bilateral and multifocal involvement'''
** '''Mutation: VHL'''
** '''<span style="color:#ff0000">Mutation: VHL</span>'''
*** '''VHL is a tumor suppressor gene,''' for both familial and sporadic ccRCC, at '''chromosome 3'''p25-26
*** '''VHL is a tumor suppressor gene,''' for both familial and sporadic ccRCC, at '''chromosome 3'''p25-26
**** '''VHL mutation is most common genetic mutation in sporadic RCC'''§
**** '''<span style="color:#ff0000">VHL mutation is most common genetic mutation in sporadic RCC</span>'''§
*** Under normal conditions, the '''VHL complex targets hypoxia-inducible factors (HIF) for degradation''', keeping levels of HIF low. HIF regulates response to hypoxia, starvation, and other stresses
*** Under normal conditions, the '''<span style="color:#ff0000">VHL complex targets hypoxia-inducible factors (HIF) for degradation</span>''', keeping levels of HIF low. HIF regulates response to hypoxia, starvation, and other stresses
*** '''In the absence of VHL, HIF accumulates and leads to overexpression of vascular endothelial growth factor (VEGF), the primary angiogenic growth factor in RCC''', contributing to the neovascularity associated with ccRCC.
*** '''<span style="color:#ff0000">In the absence of VHL, HIF accumulates and leads to overexpression of vascular endothelial growth factor (VEGF), the primary angiogenic growth factor in RCC''', contributing to the neovascularity associated with ccRCC</span>.
**** Production of erythropoietin (EPO) is closely associated with circulating oxygen levels. During conditions of hypoxia, hypoxia-inducible factor-1-alpha (HIF-1-a) is upregulated increasing EPO transcription. HIF-1-a is then rapidly degraded by proteases upon restoration of normal oxygen tension.
**** Production of erythropoietin (EPO) is closely associated with circulating oxygen levels. During conditions of hypoxia, hypoxia-inducible factor-1-alpha (HIF-1-a) is upregulated increasing EPO transcription. HIF-1-a is then rapidly degraded by proteases upon restoration of normal oxygen tension.
** '''Pheochromocytoma manifestations of VHL are restricted to certain families (type 2 VHL)'''
** '''<span style="color:#ff0000">Pheochromocytoma manifestations of VHL are restricted to certain families (type 2 VHL)</span>'''
** '''Patients suspected of having VHL, or the appropriate relatives of those with documented disease, should strongly consider genetic evaluation.'''
** '''Patients suspected of having VHL, or the appropriate relatives of those with documented disease, should strongly consider genetic evaluation.'''
*** Patients with germline mutations of the VHL gene can be offered screening to identify major manifestations of VHL at a pre-symptomatic phase
*** Patients with germline mutations of the VHL gene can be offered screening to identify major manifestations of VHL at a pre-symptomatic phase
** '''RCC is most common cause of death in VHL patients'''
** '''<span style="color:#ff0000">RCC is most common cause of death in VHL patients</span>'''


* '''Hereditary Papillary Renal Cell Carcinoma (HPRCC)'''
* '''<span style="color:#ff0000">Hereditary Papillary Renal Cell Carcinoma (HPRCC)</span>'''
** Tumours tend to be '''less aggressive''' than their sporadic counterparts
** Tumours tend to be '''less aggressive''' than their sporadic counterparts
** '''Most of the mutations in HPRCC have been found in the tyrosine kinase domain of met and lead to constitutive activation of the receptor for hepatocyte growth factor'''
** '''Most of the mutations in HPRCC have been found in the tyrosine kinase domain of met and lead to <span style="color:#ff0000">constitutive activation of the receptor for hepatocyte growth factor</span>'''


* '''Hereditary leiomyomatosis and RCC syndrome (HLRCC)'''
* '''<span style="color:#ff0000">Hereditary leiomyomatosis and RCC syndrome (HLRCC)</span>'''
** '''Almost all individuals with this syndrome will develop cutaneous leiomyomas and uterine fibroids (if female),''' usually manifesting at the age of 20-35 years.
** '''<span style="color:#ff0000">Almost all individuals with this syndrome will develop cutaneous leiomyomas and uterine fibroids (if female),</span>''' usually manifesting at the age of 20-35 years.
*** '''A high proportion of women have had a hysterectomy for fibroids before formal diagnosis of HLRCC'''.
*** '''A high proportion of women have had a hysterectomy for fibroids before formal diagnosis of HLRCC'''.
** '''Only a minority (20%) of HLRCC patients develop RCC'''
** '''Only a minority (20%) of HLRCC patients develop RCC'''
*** Penetrance for RCC in HLRCC is lower than for the cutaneous and uterine manifestations
*** Penetrance for RCC in HLRCC is lower than for the cutaneous and uterine manifestations
** Unlike other familial syndromes, '''tumours with this syndrome tend to be unilateral, solitary, and''' '''more aggressive'''; therefore, '''prompt surgical management is indicated'''
** Unlike other familial syndromes, '''tumours with this syndrome tend to be unilateral, solitary, and''' '''<span style="color:#ff0000">more aggressive</span>'''; therefore, '''prompt surgical management is indicated'''


* '''Tuberous Sclerosis Complex (TSC)'''
* '''Tuberous Sclerosis Complex (TSC)'''
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