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PIK3CA and AKT1 mutations in hidradenoma papilliferum
  1. Keisuke Goto1,2,
  2. Daichi Maeda3,
  3. Yukitsugu Kudo-Asabe3,
  4. Takashi Hibiya4,
  5. Akimasa Hayashi5,
  6. Masashi Fukayama5,
  7. Kenichi Ohashi4,
  8. Akiteru Goto3
  1. 1Department of Diagnostic Pathology, Kainan Hospital, Aichi, Japan
  2. 2Department of Pathology and Cytology, Karolinska University Hospital, Stockholm, Sweden
  3. 3Department of Cellular and Organ Pathology, Graduate School of Medicine, Akita University, Akita, Japan
  4. 4Department of Pathology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan
  5. 5Department of Pathology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
  1. Correspondence to Dr Daichi Maeda, Department of Cellular and Organ Pathology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita-shi, Akita 010-8543, Japan; maeda-tky{at}umin.ac.jp

Abstract

Aims Hidradenoma papilliferum (HP) is a benign vulvar neoplasm that arises from anogenital mammary-like glands, and its morphology is similar to mammary intraductal papilloma. The aim of this study was to investigate oncogenic mutations involved in the tumourigenesis of HP. We focused specifically on PIK3CA and AKT1 mutations, which are both reported to be detected in 33% of mammary intraductal papillomas.

Methods In total, seven HP cases were analysed. Clinicopathological analyses and immunohistochemistry for oestrogen receptor, p63, smooth muscle actin (SMA), p53 and β-catenin were performed. Furthermore, PIK3CA, AKT1, BRAF and KRAS hot spot mutations were examined by Sanger sequencing.

Results Morphologically, all HPs had a papillary and tubular architecture with a biphasic pattern of epithelial and myoepithelial cells. Immunohistochemistry revealed that oestrogen receptor expression was restricted to epithelial cells, whereas p63 and SMA were exclusively expressed in myoepithelial cells. The patterns of p53 and β-catenin immunostaining suggested wild-type genotypes. Direct sequencing revealed the presence of somatic PIK3CA mutations (Ex9. c.1633G>A, p.E545K and Ex20. c.3140A>G, p.H1047R) in two of the HPs and an AKT1 (c.49G>A, p.E17K) mutation in one. BRAF and KRAS mutations were not found in any of the HP cases.

Conclusions PIK3CA and AKT1 are frequently mutated in HP tumours (29% and 14%, respectively). PIK3CA/AKT1 pathway alterations in HP further support the hypothesis that HP is the vulvar (anogenital mammary-like gland) analogue of breast intraductal papilloma.

  • GYNAECOLOGICAL PATHOLOGY
  • SKIN TUMOURS
  • GENETICS
  • IMMUNOHISTOCHEMISTRY

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Footnotes

  • KG and DM contributed equally.

  • Handling editor Cheok Soon Lee

  • Contributors KG, DM, MF, KO and AG designed the study. KG, DM, YA-K, TH and AH performed experiments and pathological analysis. KG and DM drafted the manuscript. AG critically read the draft and gave comments.

  • Funding This work was supported by a Grant-in-Aid for Scientific Research (KAKENHI), No. 16K08646, from the Japan Society for the Promotion of Science.

  • Competing interests None declared.

  • Ethics approval Akita University, Yokohama City University, Kainan Hospital.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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