PMID- 32796174
OWN - NLM
STAT- MEDLINE
DCOM- 20211109
LR  - 20211109
IS  - 1533-0311 (Electronic)
IS  - 0193-1091 (Linking)
VI  - 43
IP  - 4
DP  - 2021 Apr 1
TI  - Hedgehog Pathway Alterations Downstream of Patched-1 Are Common in 
      Infundibulocystic Basal Cell Carcinoma.
PG  - 266-272
LID - 10.1097/DAD.0000000000001746 [doi]
AB  - The infundibulocystic variant of basal cell carcinoma (BCC) is characterized 
      histologically by anastamosing strands of basaloid epithelium with associated 
      small infundibular-type cysts. Since its first description in 1987, this rare 
      entity has generated considerable controversy with some authors classifying it as 
      a benign follicular neoplasm rather than a BCC subtype. Prior studies aiming to 
      settle this issue using immunohistochemical analysis reached opposite 
      conclusions. The defining feature of BCC is activation of the Hedgehog signaling 
      pathway, and mutations in Patched-1 (PTCH1) are the most common molecular finding 
      in both sporadic and inherited forms of BCC. Mutations in other downstream 
      components including Smoothened (SMO) and Suppressor of Fused (SUFU) also occur, 
      but are much less common. Here, we report a molecular genetic analysis of a small 
      series of infundibulocystic BCC using a next-generation DNA sequencing platform. 
      All 4 cases harbored mutations or other genetic alterations in components of the 
      Hedgehog pathway, supporting the classification of this entity as a BCC variant. 
      Interestingly, these tumors were enriched for genetic alterations downstream of 
      PTCH1, involving SUFU, SMO, GLI1, and GLI2. This observation was of particular 
      interest given that rare kindreds of the Multiple Hereditary Infundibulocystic 
      BCC syndrome (MHIBCC), which is related, but possibly distinct from the nevoid 
      BCC syndrome, harbored mutations in SUFU. Our results support the classification 
      of the infundibulocystic variant as a subtype of BCC, and suggest that the level 
      at which genetic alterations occur within the Hedgehog pathway may be an 
      important determinant of the morphologic features in BCC.
CI  - Copyright (c) 2020 Wolters Kluwer Health, Inc. All rights reserved.
FAU - Russell-Goldman, Eleanor
AU  - Russell-Goldman E
AD  - Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, 
      Boston, MA.
FAU - MacConaill, Laura
AU  - MacConaill L
FAU - Hanna, John
AU  - Hanna J
LA  - eng
PT  - Case Reports
PT  - Journal Article
PL  - United States
TA  - Am J Dermatopathol
JT  - The American Journal of dermatopathology
JID - 7911005
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (GLI1 protein, human)
RN  - 0 (GLI2 protein, human)
RN  - 0 (Nuclear Proteins)
RN  - 0 (PTCH1 protein, human)
RN  - 0 (Patched-1 Receptor)
RN  - 0 (Repressor Proteins)
RN  - 0 (SMO protein, human)
RN  - 0 (SUFU protein, human)
RN  - 0 (Smoothened Receptor)
RN  - 0 (Zinc Finger Protein GLI1)
RN  - 0 (Zinc Finger Protein Gli2)
RN  - Basal cell carcinoma, infundibulocystic
SB  - IM
MH  - Biomarkers, Tumor/*genetics
MH  - Carcinoma, Basal Cell/*genetics/pathology
MH  - DNA Mutational Analysis
MH  - High-Throughput Nucleotide Sequencing
MH  - Humans
MH  - *Mutation
MH  - Nuclear Proteins/genetics
MH  - Patched-1 Receptor/*genetics
MH  - Repressor Proteins/genetics
MH  - Retrospective Studies
MH  - Skin Neoplasms/*genetics/pathology
MH  - Smoothened Receptor/genetics
MH  - Zinc Finger Protein GLI1/genetics
MH  - Zinc Finger Protein Gli2/genetics
COIS- The authors declare no conflicts of interest.
EDAT- 2020/08/17 06:00
MHDA- 2021/11/10 06:00
CRDT- 2020/08/16 06:00
PHST- 2020/08/17 06:00 [pubmed]
PHST- 2021/11/10 06:00 [medline]
PHST- 2020/08/16 06:00 [entrez]
AID - 00000372-202104000-00004 [pii]
AID - 10.1097/DAD.0000000000001746 [doi]
PST - ppublish
SO  - Am J Dermatopathol. 2021 Apr 1;43(4):266-272. doi: 10.1097/DAD.0000000000001746.