Renal disease in adults with TSC2/PKD1 contiguous gene syndrome

Guido Martignoni, Franco Bonetti, Maurizio Pea, Regina Tardanico, Matteo Brunelli, John Eble

Research output: Contribution to journalArticle

69 Citations (Scopus)

Abstract

The most common renal lesions of tuberous sclerosis complex, an autosomal-dominant syndrome resulting from losses of TSC1 (9q34) or TSC2 (16p13.3), are renal cysts and angiomyolipomas. Epithelial neoplasms are less common. The TSC2 gene lies adjacent to PKD1, the major gene responsible for autosomal-dominant polycystic kidney disease. Recently, a deletion mutation disrupting both TSC2 and PKD1 has been described in young children with tuberous sclerosis complex with severe renal cystic disease. This disease has been termed the TSC2/PKD1 contiguous gene syndrome. We describe the lesions in the resected kidneys of two adults with TSC2/PDK1 contiguous gene syndrome, at the time of the nephrectomies: a 31-year-old man and his 44-year-old mother. The four kidneys were enlarged reniform masses composed of cysts lined by flattened, cuboidal, or, infrequently, large deeply eosinophilic epithelial cells. The kidneys also contained numerous classic angiomyolipomas and rare intraglomerular microlesions. In the son the largest tumor was a monotypic epithelioid angiomyolipoma. In the wall of his left renal pelvis there was a plaque-shaped, HMB-45-positive localized lesion of lymphangioleiomyomatosis. This is the first description of the renal lesions in adults with genetically confirmed TSC2/PDK1 contiguous gene syndrome. The pathologic findings highlight the importance of thorough sampling for histology in polycystic kidney diseases and indicate that the observation of an angiomyolipoma in biopsy material from patients with enlarged cystic kidneys should suggest the diagnosis of TSC2/PKD1 contiguous gene syndrome, even in cases without ultrasonographic and macroscopic evidence of angiomyolipoma.

Original languageEnglish (US)
Pages (from-to)198-205
Number of pages8
JournalAmerican Journal of Surgical Pathology
Volume26
Issue number2
DOIs
StatePublished - 2002
Externally publishedYes

Fingerprint

Angiomyolipoma
Kidney
Genes
Cystic Kidney Diseases
Tuberous Sclerosis
Cysts
Lymphangioleiomyomatosis
Autosomal Dominant Polycystic Kidney
Polycystic Kidney Diseases
Kidney Pelvis
Glandular and Epithelial Neoplasms
Sequence Deletion
Nephrectomy
Nuclear Family
Histology
Epithelial Cells
Mothers
Observation
Biopsy
Neoplasms

Keywords

  • Angiomyolipoma
  • Autosomal-dominant polycystic kidney disease
  • Contiguous TSC2 and PKD1 gene syndrome
  • Epithelioid
  • HMB45
  • Lymphangioleiomyomatosis
  • Perivascular epithelioid cell
  • Tuberous sclerosis

ASJC Scopus subject areas

  • Anatomy
  • Pathology and Forensic Medicine

Cite this

Renal disease in adults with TSC2/PKD1 contiguous gene syndrome. / Martignoni, Guido; Bonetti, Franco; Pea, Maurizio; Tardanico, Regina; Brunelli, Matteo; Eble, John.

In: American Journal of Surgical Pathology, Vol. 26, No. 2, 2002, p. 198-205.

Research output: Contribution to journalArticle

Martignoni, Guido ; Bonetti, Franco ; Pea, Maurizio ; Tardanico, Regina ; Brunelli, Matteo ; Eble, John. / Renal disease in adults with TSC2/PKD1 contiguous gene syndrome. In: American Journal of Surgical Pathology. 2002 ; Vol. 26, No. 2. pp. 198-205.
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AU - Pea, Maurizio

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AU - Brunelli, Matteo

AU - Eble, John

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AB - The most common renal lesions of tuberous sclerosis complex, an autosomal-dominant syndrome resulting from losses of TSC1 (9q34) or TSC2 (16p13.3), are renal cysts and angiomyolipomas. Epithelial neoplasms are less common. The TSC2 gene lies adjacent to PKD1, the major gene responsible for autosomal-dominant polycystic kidney disease. Recently, a deletion mutation disrupting both TSC2 and PKD1 has been described in young children with tuberous sclerosis complex with severe renal cystic disease. This disease has been termed the TSC2/PKD1 contiguous gene syndrome. We describe the lesions in the resected kidneys of two adults with TSC2/PDK1 contiguous gene syndrome, at the time of the nephrectomies: a 31-year-old man and his 44-year-old mother. The four kidneys were enlarged reniform masses composed of cysts lined by flattened, cuboidal, or, infrequently, large deeply eosinophilic epithelial cells. The kidneys also contained numerous classic angiomyolipomas and rare intraglomerular microlesions. In the son the largest tumor was a monotypic epithelioid angiomyolipoma. In the wall of his left renal pelvis there was a plaque-shaped, HMB-45-positive localized lesion of lymphangioleiomyomatosis. This is the first description of the renal lesions in adults with genetically confirmed TSC2/PDK1 contiguous gene syndrome. The pathologic findings highlight the importance of thorough sampling for histology in polycystic kidney diseases and indicate that the observation of an angiomyolipoma in biopsy material from patients with enlarged cystic kidneys should suggest the diagnosis of TSC2/PKD1 contiguous gene syndrome, even in cases without ultrasonographic and macroscopic evidence of angiomyolipoma.

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KW - Perivascular epithelioid cell

KW - Tuberous sclerosis

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