Pathology Notes

Nevoid basal cell carcinoma syndrome Updated: 05/19/2020 © Jun Wang, MD, PhD General features AKA Gorlin syndrome, basal cell nevus syndrome, etc Autosomal dominant  Germline mutation of PTCH1 Multiple developmental abnormalities Increased risk for childhood medulloblastoma Pathogenesis Inactivation of PTCH1, receptor for hedgehog protein Loss of suppression of Smoothened (SMO) Probably downstream over activation of transcription factors Gli1 and/or Gli2 Clinical presentations Major manifestations Early development of basal cell carcinoma Odontogenic keratocyst Palmar and plantar pits Lamellar calcification of the falx cerebri Family history of nevoid basal cell carcinoma syndrome   Minor manifestations Childhood medulloblastomas Craniofacial anomalies: Cleft lip/palate, macrocephaly, frontal bossing , hypertelorism Vertebral/rib anomalies, such as bifid/splayed/extra ribs or bifid vertebrae Polydactyly Cardiac or ovarian fibromas , often b

Waterhouse Frederichsen syndrome   Updated: 06/21/2022 © Jun Wang, MD, PhD General features Adrenal insufficiency Due to bilateral/unilateral adrenal hemorrhage Associated with bacterial or viral infection   Commonly associated with meningococcal infection  Other associated pathogens include Haemophilus influenzae Pseudomonas aeruginosa Escherichia coli Streptococcus pneumoniae Pathogenesis Clinical presentations Sudden onset Nonspecific presentations: headache, fever, weakness, abdominal/flank pain, anorexia, etc Signs of shock : Tachycardia, hypotension, etc Abdominal rigidity or rebound tenderness If associated with meningococcemia: petechial rash , purpura fulminans, other neurological abnormalities Key Laboratory findings Features of Disseminated intravascular coagulation Leukocytosis Hyponatremia and hyperkalemia: Mineralocorticoid deficiency Hypoglycemia: glucocorticoid deficiency Elevated : ACTH, renin Decreased : Aldosterone, glucocortico

Cowden syndrome   Updated: 02/14/2020 © Jun Wang, MD, PhD General features Autosomal dominant most common De novo mutation occasionally More common in female Clinical presentations Mucocutaneous: Trichilemmomas , acral keratoses Breast: Breast cancer most common malignancy in patients with Cowden syndrome Thyroid: Multinodular goiter , Hashimoto thyroiditis , follicular adenoma , non-medullary carcinoma GU system: Renal cell carcinoma , Endometrial adenocarcinoma , uterine leiomyoma , testicle lipomatosis GI system: Esophageal glycogen acanthosis, Gastric and duodenal polyps, colon polyps, colorectal adenocarcinoma , Neurological: tumors including dysplastic gangliocytoma, vascular malformation, macrocephaly, mental retardation and developmental delay Immune dysregulation: B or T cell abnormalities including autoimmunity, thymus hyperplasia, etc Genetic abnormalities PTEN Diagnosis Individual diagnosis At least three major criteria (must include ma

Muir-Torre Syndrome   Updated: 01/28/20 © Jun Wang, MD, PhD General features Commonly autosomal dominant syndrome Combination of neoplasms of the skin and a visceral malignancy Likely a subtype of hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome ) Clinical presentations Skin neoplasia Sebaceous adenoma /carcinoma Sebaceous epithelioma Keratoacanthoma Visceral malignancies Colorectal Endometrial Small intestine Urothelial Genetic abnormalities MSH2, most common Other DNA mismatch repair gene (MMR) MUTYH: Muir-Torre Syndrome II, autosomal recessive Diagnosis Clinical criteira, suspected if presents with one or more of the following   Sebaceous tumor <60 when first sebaceous tumor presents Personal or family history of Lynch-related tumors Tumor testing Immunohistochemistry for MMRs Microsatellite instability analysis MUTYH Germline mutation analysis: If tumor testing indicative of MMR mutation Manageme