Neurosurgery notes/Tumours/Tumour syndrome/Cowden syndrome

Cowden syndrome

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Tumour syndrome

General

  • Classically associated with trichilemmoma (benign cutaneous neoplasm that shows differentiation toward cells of the outer root sheath of the hair follicle)
      • Multiple trichilemmomas in patient with Cowden dis
       
      Close-up of a person's nose and mouth AI-generated content may be incorrect.
  • There is diagnostic criteria that is quite complex i doubt we need to know that

Definition

  • Autosomal dominant disorder characterized by multiple hamartomas involving tissues derived from all three germ cell layers

Numbers

  • Incidence 1/200k
  • Presents at 30 yrs old

Site of involvement

Lhermitte-Duclos disease

  • Enlarged brain (megalencephaly)
  • Hydromyelia
  • Extra fingers or toes (polydactyly)
  • Partial gigantism, and/or a
  • Large tongue (macroglossia)

Additional symptoms

  • Cancers (most common to least)
      • Cancer type
      Lifetime risk
      Breast Ca
      25-85%
      Thyroid Ca
      10-35%
      Colorectal Ca
      9%-16%
  • Mucocutaneous lesions
      • Palmar keratosis
      Close-up of a person's skin AI-generated content may be incorrect.
       
  • Non-malignant thyroid abnormalities
  • Fibrocystic disease of the breast
  • Gastrointestinal hamartomas
  • Early-onset uterine leiomyomas
  • Macrocephaly
  • Mental retardation

Genetic

  • PTEN
      • 10q23.3
      • PTEN mutation identified in all adult diseases → adult and children have very different pathogenetics
      • PTEN when mutated will affect downstream pathways PI3K/AKT pathway
      • Tumour suppressor
      • Dual-specificity lipid phosphatase that plays multiple roles in the cell cycle, apoptosis, cell polarity, cell migration, and even genomic stability
      P13K Survival AKT mTOR PTEN Migration Angiogenesis Proliferation Fig. 16.25 Schematic representation of the P13K/AKT/ m TOR signalling pathway. When P TEN is downregulated, AK T is Upregulated, leading to upregulation of m TOR. Reprinted from Blumenthal GM and Dennis PA {220}.
      Schematic representation of the PI3K/AKT/mTOR signalling pathway. When PTEN is downregulated, AKT is Upregulated, leading to upregulation of mTOR. Reprinted from Blumenthal GM and Dennis PA {220}.
  • Other genes less common
    • SDH
    • PIK3CA
    • AKT1
    • KLLN

PTEN Hamartoma tumor syndrome

  • Cowden syndrome: multiple hamartoma syndrome, benign and malignant tumors of the thyroid, breast, and endometrium
  • Bannayan-riley-ruvalcaba syndrome: macrocephaly, intestinal hamartomatous polyposis, lipomas, and pigmented macules of the glans penis
  • PTEN-related proteus syndrome and proteus-like syndrome
PTEN HAMARTOMA TUMOR SYNDROME AD cancer-predisposition syndrome • COWDEN SYNDROME : multiple hamartoma syndrome, benign and malignant tumors of the thyroid, breast, and endometrium • BANNAYAN-RILEY-RUVALCABA SYNDROME: macrocephaly, intestinal hamartomatous polyposis, lipomas, and pigmented macules of the glans penis • PTEN-RELATED PROTEUS SYNDROME and PROTEUS-LIKE SYNDROME 4 DYSPLASTIC GANGLIOCYTOMA OF THE CEREBELLUM LHERMIHE-DUCLOS DISEASE Bosemani et Al Neuroimag Clin N Am 2016
Dysplastic gangliocytoma of the cerebellum (Lhermite-duclose disease)

Images

PhaWnatosis mTOR & RAS PATHWAYS KEY CELL SIGNALING PATHWAYS (isc 13 HRAS KRAS Gene transcription r.vus SOLAMEN AUTOSOMAL DOMINANT MUTATION Protein translation