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Abnormal Cystic Tumor in a Patient with Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome: Evidence of a Precursor Lesion?

Ristau BT, Kamat SN, Tarin TV - Case Rep Urol (2015)

Bottom Line: Its absence leads to a state of "pseudohypoxia," inducing hypoxia inducible factor 1α (HIF-1α) and leading to increased growth factor transcription (e.g., vascular endothelial growth factor, VEGF; glucose transporter 1, GLUT1).Ultimately, this results in tumorigenesis.One of the nephrectomy specimens was notable for benign cystic lesions that stained positive immunohistochemically for succinated proteins, a finding only noted in FH-deficient cells.

View Article: PubMed Central - PubMed

Affiliation: Deparment of Urology, University of Pittsburgh Medical Center, Pittsburgh, PA 15219, USA.

ABSTRACT
The hereditary leiomyomatosis and renal cell cancer (HLRCC) association is a rare syndrome caused by mutation of the Kreb's cycle enzyme, fumarate hydratase (FH). It is characterized by unusually aggressive type 2 papillary renal cell histology. FH is responsible for catalyzing the conversion of fumarate to malate. Its absence leads to a state of "pseudohypoxia," inducing hypoxia inducible factor 1α (HIF-1α) and leading to increased growth factor transcription (e.g., vascular endothelial growth factor, VEGF; glucose transporter 1, GLUT1). Ultimately, this results in tumorigenesis. We present a patient who was diagnosed with HLRCC and underwent bilateral nephrectomies. One of the nephrectomy specimens was notable for benign cystic lesions that stained positive immunohistochemically for succinated proteins, a finding only noted in FH-deficient cells. Thus, we posit a potential precursor lesion to type 2 papillary renal cell carcinoma in the HLRCC syndrome.

No MeSH data available.


Related in: MedlinePlus

(a) Gross specimen of right radical nephrectomy demonstrating papillary renal cell carcinoma. (b) Low power H&E stained representation of papillary type 2 renal cell carcinoma. (c) H&E stained slide demonstrating papillary architecture. (d) H&E stained representtion of cytologic and nuclear atypia.
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fig2: (a) Gross specimen of right radical nephrectomy demonstrating papillary renal cell carcinoma. (b) Low power H&E stained representation of papillary type 2 renal cell carcinoma. (c) H&E stained slide demonstrating papillary architecture. (d) H&E stained representtion of cytologic and nuclear atypia.

Mentions: The patient is a 24-year-old woman at 35 weeks' gestational age that presented to the emergency department with right flank pain. An US demonstrated a 15 cm infiltrating and partially cystic right renal mass. She was induced and had an uneventful vaginal delivery. A CT scan was performed which confirmed an enhancing 15 cm right renal mass (Figure 1). She underwent right adrenal-sparing radical nephrectomy with paracaval lymphadenectomy. Final pathology from this surgery was reported as pT3aN1MX renal cell carcinoma of unclassified type (Figure 2). The histology was described as cells arranged in well-organized papillae with hobnail features, intraluminal blue secretions, villous-like architectural features, and a focus of bizarre nuclear atypia. FISH analysis was negative for trisomy 7-, trisomy 17-, and TFE3 translocation-associated renal cell carcinomas. Some tumor cells were noted to have very large eosinophilic nuclei with subtle perinuclear clearing. A suspicion for papillary type II histology was raised and the patient was referred for genetic testing. Indeed, a heterozygous 698G>A mutation was noted in the FH gene consistent with a diagnosis of HLRCC. Four months after her right nephrectomy, she underwent PET-CT imaging which demonstrated an FDG-avid left adrenal gland in addition to multiple septated left renal cysts (Figure 1). Given the known aggressive nature of HLRCC-associated type 2 papillary renal cell carcinomas, radical left nephrectomy with adrenalectomy and retroperitoneal lymph node dissection was performed and the specimen was submitted for pathologic analysis.


Abnormal Cystic Tumor in a Patient with Hereditary Leiomyomatosis and Renal Cell Cancer Syndrome: Evidence of a Precursor Lesion?

Ristau BT, Kamat SN, Tarin TV - Case Rep Urol (2015)

(a) Gross specimen of right radical nephrectomy demonstrating papillary renal cell carcinoma. (b) Low power H&E stained representation of papillary type 2 renal cell carcinoma. (c) H&E stained slide demonstrating papillary architecture. (d) H&E stained representtion of cytologic and nuclear atypia.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4561951&req=5

fig2: (a) Gross specimen of right radical nephrectomy demonstrating papillary renal cell carcinoma. (b) Low power H&E stained representation of papillary type 2 renal cell carcinoma. (c) H&E stained slide demonstrating papillary architecture. (d) H&E stained representtion of cytologic and nuclear atypia.
Mentions: The patient is a 24-year-old woman at 35 weeks' gestational age that presented to the emergency department with right flank pain. An US demonstrated a 15 cm infiltrating and partially cystic right renal mass. She was induced and had an uneventful vaginal delivery. A CT scan was performed which confirmed an enhancing 15 cm right renal mass (Figure 1). She underwent right adrenal-sparing radical nephrectomy with paracaval lymphadenectomy. Final pathology from this surgery was reported as pT3aN1MX renal cell carcinoma of unclassified type (Figure 2). The histology was described as cells arranged in well-organized papillae with hobnail features, intraluminal blue secretions, villous-like architectural features, and a focus of bizarre nuclear atypia. FISH analysis was negative for trisomy 7-, trisomy 17-, and TFE3 translocation-associated renal cell carcinomas. Some tumor cells were noted to have very large eosinophilic nuclei with subtle perinuclear clearing. A suspicion for papillary type II histology was raised and the patient was referred for genetic testing. Indeed, a heterozygous 698G>A mutation was noted in the FH gene consistent with a diagnosis of HLRCC. Four months after her right nephrectomy, she underwent PET-CT imaging which demonstrated an FDG-avid left adrenal gland in addition to multiple septated left renal cysts (Figure 1). Given the known aggressive nature of HLRCC-associated type 2 papillary renal cell carcinomas, radical left nephrectomy with adrenalectomy and retroperitoneal lymph node dissection was performed and the specimen was submitted for pathologic analysis.

Bottom Line: Its absence leads to a state of "pseudohypoxia," inducing hypoxia inducible factor 1α (HIF-1α) and leading to increased growth factor transcription (e.g., vascular endothelial growth factor, VEGF; glucose transporter 1, GLUT1).Ultimately, this results in tumorigenesis.One of the nephrectomy specimens was notable for benign cystic lesions that stained positive immunohistochemically for succinated proteins, a finding only noted in FH-deficient cells.

View Article: PubMed Central - PubMed

Affiliation: Deparment of Urology, University of Pittsburgh Medical Center, Pittsburgh, PA 15219, USA.

ABSTRACT
The hereditary leiomyomatosis and renal cell cancer (HLRCC) association is a rare syndrome caused by mutation of the Kreb's cycle enzyme, fumarate hydratase (FH). It is characterized by unusually aggressive type 2 papillary renal cell histology. FH is responsible for catalyzing the conversion of fumarate to malate. Its absence leads to a state of "pseudohypoxia," inducing hypoxia inducible factor 1α (HIF-1α) and leading to increased growth factor transcription (e.g., vascular endothelial growth factor, VEGF; glucose transporter 1, GLUT1). Ultimately, this results in tumorigenesis. We present a patient who was diagnosed with HLRCC and underwent bilateral nephrectomies. One of the nephrectomy specimens was notable for benign cystic lesions that stained positive immunohistochemically for succinated proteins, a finding only noted in FH-deficient cells. Thus, we posit a potential precursor lesion to type 2 papillary renal cell carcinoma in the HLRCC syndrome.

No MeSH data available.


Related in: MedlinePlus