Residency - Kidney and Peri-kidney Flashcards
Neuroblastoma (poorly differentiated type)
85% present in patients less than 5 years of age, ~2/3 are metastatic at the time of presentation. 4th most common tumor of children. Arise from the sympathetic chain or adrenal medulla. Liver metastases are common.
Histologically characterized by a small round blue cell tumor with neuroendocrine-type chromatin in a trabecular background with a schwannian stroma and/or neuropil. Homer-Wright rosettes (neuroblasts surrounding a central core of neurites without a central lumen) can often be seen, but are not specific.
When in bone, often paratrabecular.
Subclassificications:
Undifferentiated NB
Poorly differentiated NB (most common, shown here)
Differentiating NB
Nodular ganglioNB
Intermixed ganglioNB
IHC: Neuroendocrine marker +, NB84+, PGP9.5 +, PHOX2B+.
Molecular: MYCN amplification, TERT rearrangements, ATRX mutations. Near-dipoloid or tetraploid karyotype. Tumors null for these three gene changes have the best prognosis.
Neuroblastoma (undifferentiated type)
85% present in patients less than 5 years of age, ~2/3 are metastatic at the time of presentation. 4th most common tumor of children. Arise from the sympathetic chain or adrenal medulla. Liver metastases are common.
Histologically characterized by a small round blue cell tumor with neuroendocrine-type chromatin in a trabecular background with a schwannian stroma and/or neuropil. Homer-Wright rosettes (neuroblasts surrounding a central core of neurites without a central lumen) can often be seen, but are not specific.
When in bone, often paratrabecular.
Subclassificications:
Undifferentiated NB
Poorly differentiated NB
Differentiating NB
Nodular ganglioNB
Intermixed ganglioNB
IHC: Neuroendocrine marker +, NB84+, PGP9.5 +, PHOX2B+.
Molecular: MYCN amplification, TERT rearrangements, ATRX mutations. Near-dipoloid or tetraploid karyotype. Tumors null for these three gene changes have the best prognosis.
Neuroblastoma (differentiating type)
85% present in patients less than 5 years of age, ~2/3 are metastatic at the time of presentation. 4th most common tumor of children. Arise from the sympathetic chain or adrenal medulla. Liver metastases are common.
Histologically characterized by a small round blue cell tumor with neuroendocrine-type chromatin in a trabecular background with a schwannian stroma and/or neuropil. Homer-Wright rosettes (neuroblasts surrounding a central core of neurites without a central lumen) can often be seen, but are not specific.
When in bone, often paratrabecular.
Subclassificications:
Undifferentiated NB
Poorly differentiated NB
Differentiating NB
Nodular ganglioNB
Intermixed ganglioNB
IHC: Neuroendocrine marker +, NB84+, PGP9.5 +, PHOX2B+.
Molecular: MYCN amplification, TERT rearrangements, ATRX mutations. Near-dipoloid or tetraploid karyotype. Tumors null for these three gene changes have the best prognosis.
Typical course for a neuroblastoma
Treated with neoadjuvant chemotherapy followed by surgery after 3-4 months.
Histologically, the chemotherapy frequently results in necrosis, hemosiderin deposition, fibrosis, calcification, and varying degrees of tumor maturation / gangliocytic differentiation.
Staging of a neuroblastoma (INSS system)
Neuroblastoma is currently staged by two systems: the International Neuroblastoma Staging System (INSS) and International Neuroblastoma Risk Group Staging System (INRG). Of the two, the INRG is more recent.
The INSS must be applied post-resection for accurate staging, while the INRG must be applied pre-resection for accurate staging.
Staging of a neuroblastoma (INRG system)
Neuroblastoma is currently staged by two systems: the International Neuroblastoma Staging System (INSS) and International Neuroblastoma Risk Group Staging System (INRG). Of the two, the INRG is more recent.
The INSS must be applied post-resection for accurate staging, while the INRG must be applied pre-resection for accurate staging.
When neuroblastoma cells differentiated, they differentiated towards . . .
. . . ganglion cells.
Neuroblastoma in-situ
An incidental finding at autopsy in 0.4-2.5% of intants younger than 3 months.
May not be neoplastic or may mature into a ganglioneuroma.
Characterized by clusters of immature neuroblasts, ranging from 0.7 to 9.5 mm, frequently with cystic change.
Ganglioneuroblastoma (intermixed type)
60-70% are advanced stage (stage 3 or 4) or have metastases at the time of diagnosis.
Ganglioneuroblastoma displays a level of maturation and differentiation intermediate between the highly aggressive neuroblastoma and the benign ganglioneuroma. All three entities exist on a contiuum both morphologically and genetically. There is a histologic overlap between differentiating neuroblastoma and ganglioneuroblastoma.
Ganglioneuroblastomas are divided into two types: Intermixed and nodular. Nodular ganglioneuroblastomas are composite tumors that have a well-defined highly cellular area of neuroblastoma in a background of a ganglioneuroma. Intermixed ganglioneurlboastomas show a mixture of the two cell types with different stages of neuronal differentiation scattered in a background of neuropil.
Histologically, composed of neuroblasts and ganglion cells, similar to neuroblastoma. Homer-Wright bodies may also be present. Differentiating neuroblasts have moderate to abundant acidophilic or amphophilic cytoplasm and an enlarged eccentric vesicular nucleus with a single prominent nucleolus. The ganglion cells may be immature, multinucleated, or morphologically abnormal. The background consists of a fine, fibrillary network (neuropil) composed of abundant neurites arising from the differentiating ganglion cells. Calcification is a common finding.
IHC: Neuron-specific enolase +, CD57/Leu7 +, CD56+, PGP9.5+, neuroendocrine marker +, ALK1+, PHOX2B+
Molecular: Thought to be driven by ALK gene mutation. 90% are ALK+ by IHC.
Ganglioneuroblastoma (nodular type)
60-70% are advanced stage (stage 3 or 4) or have metastases at the time of diagnosis.
Ganglioneuroblastoma displays a level of maturation and differentiation intermediate between the highly aggressive neuroblastoma and the benign ganglioneuroma. All three entities exist on a contiuum both morphologically and genetically. There is a histologic overlap between differentiating neuroblastoma and ganglioneuroblastoma.
Ganglioneuroblastomas are divided into two types: Intermixed and nodular. Nodular ganglioneuroblastomas are composite tumors that have a well-defined highly cellular area of neuroblastoma in a background of a ganglioneuroma. Intermixed ganglioneurlboastomas show a mixture of the two cell types with different stages of neuronal differentiation scattered in a background of neuropil.
Histologically, composed of neuroblasts and ganglion cells, similar to neuroblastoma. Homer-Wright bodies may also be present. Differentiating neuroblasts have moderate to abundant acidophilic or amphophilic cytoplasm and an enlarged eccentric vesicular nucleus with a single prominent nucleolus. The ganglion cells may be immature, multinucleated, or morphologically abnormal. The background consists of a fine, fibrillary network (neuropil) composed of abundant neurites arising from the differentiating ganglion cells. Calcification is a common finding.
IHC: Neuron-specific enolase +, CD57/Leu7 +, CD56+, PGP9.5+, neuroendocrine marker +, ALK1+, PHOX2B+
Molecular: Thought to be driven by ALK gene mutation. 90% are ALK+ by IHC.
Ganglioneuroma
Composed of longitudinal and transversely oriented bundles of Schwann cells in a myxoid stroma. Relatively mature ganglion cells are scattered throughout the tumor in small nests and clusters. There may be considerable variation in the distribution and density of ganglion cells. The ganglion cells are not fully mature and lack satellite cells and Nissl bodies. They contain one to three nuclei and may show mild to moderate atypia.
Rare cases may undergo sarcomatous transformation into an MPNST. Rare case reports of composite ganglioneuroma-pheochromocytoma exist. Rare case reports of Leydig cells present in a ganglioneuroma with female virilization also exist.
von Hippel Lindau syndrome
Caused by mutations in the VHL gene, a regulator of HIF1a.
Autosomal dominant syndrome where patients develop numerous hemangiomablastomas of the cerebellum and retina, pheochromocytoma, innear ear tumors, and clear cell renal cell carcinomas.
Also have numerous neoplastic and nonneoplastic clear cells.
Hereditary papillary RCC syndrome
Autosomal dominant syndrome caused by mutatuins in the MET gene.
Characterized by multiple, bilateral papillary RCCs.
Birt-Hogg-Dube syndrome
Autosomal dominant syndrome with incomplete penetrance caused by mutations in FCLN (folliculin) and characterized by multiple cutanensou hamartomas (fibrofolliculomas), pulmonary cysts, and renal tumors.
Multiple and bilateral diverse types of renal tumors are present, with chromophobe RCC being the most common. Oncocytoma, papillary RCC, and clear cell tumors can be seen as well.
Tuberous sclerosis complex
Autosomal dominant syndrome with incomplete penetrance caused by mutations in TSC1 or TSC2 and characterized by multiple hamartomas and neoplasms of the brain, eyes, skin, kidney, and heart.
Angiomyolipoma is the most common renal tumor in TSC, followed by oncocytoma and RCC.
