Acquired resistance to the Hedgehog pathway inhibitor vismodegib due to smoothened mutations in treatment of locally advanced basal cell carcinoma Tjinta.

Slides:

Advertisements

Similar presentations

Topically applied ascorbic acid solution for the treatment of basal cell carcinoma (BCC) Péter Holló, MD, PhD, Hajnalka Jókai, MD, PhD, Judit Hársing,

Advertisements

Steven Q. Wang, MD, Leonard H. Goldberg, MD, FRCP

Calcific elastosis in the setting of weight gain

Intradermal injection of autologous platelet-rich plasma for the treatment of vulvar lichen sclerosus Andrew T. Goldstein, MD, Michelle King, MSc, Charles.

Systematized linear porokeratosis: A rare variant of diffuse porokeratosis with good response to systemic acitretin Jin-Bon Hong, MD, Cheng-Hsiang Hsiao,

Evaluation of skin atrophy associated with linear atrophoderma of Moulin by ultrasound imaging Osamu Norisugi, MD, Teruhiko Makino, MD, PhD, Hiroshi.

Cutaneous vasculitis in two patients taking an herbal supplement containing black cohosh Adam Ingraffea, BA, Kevin Donohue, MD, Caroline Wilkel, MD,

Accuracy of biopsy sampling for subtyping basal cell carcinoma

Volume 3, Issue 3, Pages (May 2017)

Diffuse hyperpigmented plaques as cutaneous manifestation of multicentric Castleman disease and treatment with thalidomide: Report of three cases Xiaoqing.

Squamous cell carcinoma over tattoos

Expression of PD-L1 in mastocytosis

Idiopathic eruptive macular pigmentation associated with pregnancy and Hashimoto thyroiditis Danica Milobratovic, MD, Sanja Djordjevic, MD, Jelica Vukicevic,

Palisaded neutrophilic and granulomatous dermatitis associated with limited systemic sclerosis Basil M. Hantash, MD, PhD, David Chiang, Sabine Kohler,

Peter C. Schalock, MD, Jeoffrey B. Brennick, MD, James G. H

Pigmentation after using topical tacrolimus to treat lichen sclerosus: Possible role of stem cell factor Young Jin Kim, MD, Hee Young Kang, MD, PhD

Primary thyroid marginal zone B-cell lymphoma in a patient with psoriatic arthritis treated with etanercept Hyunju Jin, MD, Hyun-Ho Cho, MD, Won-Jeong.

Cholangiocarcinoma with skin metastases

Rapid deterioration in a patient with primary aggressive cutaneous epidermotropic CD8+ cytotoxic T-cell (‘Berti’) lymphoma after administration of adalimumab

Squamous cell carcinoma tumor thrombus encountered during Mohs micrographic surgery Gary Mendese, MD, Jeremy Bordeaux, MD, MPH, Sean Pattee, MD, Mary.

Tuberculous cellulitis as a manifestation of miliary tuberculosis in a patient with malignancy-associated dermatomyositis Ji Eun Kim, MD, Joo Yeon Ko,

Major response to vemurafenib in patient with severe cutaneous Langerhans cell histiocytosis harboring BRAF V600E mutation Julie Charles, MD, PhD, Jean-Claude.

Atypical lymphocytic reaction with epidermotropism and lymphocytic vasculopathic reaction (lymphocytic vasculitis) after treatment with imiquimod Jesús.

Pink pigtails are a clue for the diagnosis of scabies

Development of a reticular rash in a febrile woman: An unusual cutaneous presentation of angioimmunoblastic T-cell lymphoma Michelle S. Min, MSci, Jonathan.

Rachel L. Kyllo, BS, Mary Kendall Parker, MD, Ilana Rosman, MD, Amy C

Breast carcinoma masquerading as basal cell carcinoma of the nipple

Enhancing techniques to evaluate tumor margins

Digital metastasis of tongue squamous cell carcinoma

Myiasis in a giant squamous cell carcinoma

Multiple Lung Adenocarcinomas Associated With Von Hippel-Lindau Disease Koei Ikeda, MD, PhD, Hironobu Osumi, MD, Kentaro Matsuishi, MD, Eri Matsubara,

Tubular apocrine adenoma clinically and dermoscopically mimicking basal cell carcinoma Takamasa Ito, MD, Toshifumi Nomura, MD, PhD, Yasuyuki Fujita,

Solitary mastocytoma in an adult with an unusual clinical presentation

“Strawberry gums” in sarcoidosis

Volume 3, Issue 6, Pages (November 2017)

Incidental regression of an advanced basal cell carcinoma after ipilimumab exposure for metastatic melanoma Shalini V. Mohan, MD, Karen Y. Kuo, MD, Anne.

Standard step sectioning of skin biopsy specimens diagnosed as superficial basal cell carcinoma frequently yields deeper and more aggressive subtypes

Bullous rheumatoid neutrophilic dermatosis

Natural killer cell response is a predictor of good outcome in MCPyV+ Merkel cell carcinoma: A case series of 23 patients Valerie Laniosz, MD, PhD, Oluwakemi.

Volume 2, Issue 6, Pages (November 2016)

A rare case of super giant basal cell carcinoma

The merits of adding toluidine blue–stained slides in Mohs surgery in the treatment of a microcystic adnexal carcinoma Steven Q. Wang, MD, Leonard H.

Volume 4, Issue 5, Pages (June 2018)

Lip edema Journal of the American Academy of Dermatology

Genital edema in childhood: Harbinger of Crohn’s disease?

Solomon Shockman, MD, Lauren Krug, MD, Nektarios Lountzis, MD

Intradermal injection of autologous platelet-rich plasma for the treatment of vulvar lichen sclerosus Andrew T. Goldstein, MD, Michelle King, MSc, Charles.

Infliximab in the treatment of a child with cutaneous granulomas associated with ataxia telangiectasia Angana Mitra, MBChB, Jimmy Gooi, MBChB, Jonathan.

The pathophysiologic basis of scabietic nodules

Volume 4, Issue 1, Pages (January 2018)

Volume 3, Issue 4, Pages (July 2017)

Treatment of Kimura disease with mycophenolate mofetil monotherapy

Lauren R. Penzi, MD, Arturo Saavedra, MD, PhD, Maryanne M. Senna, MD

Olga Vornicova, MD, Gil Bar-Sela, MD JAAD Case Reports

Ex vivo confocal microscopy of basal cell carcinoma on a 3-color scale

Spontaneous resolution of advanced basal cell carcinoma after short-pulse treatment with hedgehog pathway inhibitor Audrey A. Jacobsen, BA, John Strasswimmer,

Multisystemic Langerhans cell histiocytosis in an adult

Expanded access study of patients with advanced basal cell carcinoma treated with the Hedgehog pathway inhibitor, vismodegib Anne Lynn S. Chang, MD,

Subcutaneous sarcoidosis presenting after treatment of Cushing's disease Jill C. Fichtel, MD, Anna Kay Wiggins Duckworth, MD, Temitope Soares, PharmD,

Jose Fernández-Vozmediano, PhD, Jose Armario-Hita, MD

Digital photography in the diagnosis of scabies

Violaceous plaque on the forehead clinically resembling angiosarcoma: Cutaneous metastasis in a patient with prostatic adenocarcinoma John S. Boswell,

Volume 3, Issue 6, Pages (November 2017)

Atypical Mycobacterium furunculosis occurring after pedicures

Volume 4, Issue 1, Pages (January 2018)

Grace A. Hile, BS, Lori Lowe, MD, J. Michelle Kahlenberg, MD, PhD

Topically applied ascorbic acid solution for the treatment of basal cell carcinoma (BCC) Péter Holló, MD, PhD, Hajnalka Jókai, MD, PhD, Judit Hársing,

Blue nodule on the finger

Volume 3, Issue 4, Pages (July 2017)

Diane M. Reisinger, MD, Armand B. Cognetta, MD, L

Presentation transcript:

Acquired resistance to the Hedgehog pathway inhibitor vismodegib due to smoothened mutations in treatment of locally advanced basal cell carcinoma Tjinta Brinkhuizen, MD, Marie G. Reinders, MD, Michel van Geel, MD, PhD, Annelot J.L. Hendriksen, MD, Aimée D.C. Paulussen, MD, PhD, Véronique J. Winnepenninckx, MD, PhD, Kristien B. Keymeulen, MD, PhD, Patricia M.M.B. Soetekouw, MD, PhD, Maurice A.M. van Steensel, MD, PhD, Klara Mosterd, MD, PhD Journal of the American Academy of Dermatology Volume 71, Issue 5, Pages 1005-1008 (November 2014) DOI: 10.1016/j.jaad.2014.08.001 Copyright © 2014 American Academy of Dermatology, Inc. Terms and Conditions

Fig 1 Clinical pictures and histologic examination on pretreatment and posttreatment tissue. A, Basal cell carcinoma (BCC) before treatment with vismodegib. B, Complete clinical response 16 weeks after start of treatment. C, Newly developed tumor nodules, 27 weeks after start of treatment. D, Tumor biopsy before treatment with vismodegib, showing infiltrative palisading basaloid cells reaching into the reticular dermis fitting the diagnosis of BCC. E, Biopsy from newly developed tumor nodule after 27 weeks of treatment with vismodegib, showing infiltrative basal cell carcinoma. F, Biopsy of responding tissue after 27 weeks of vismodegib, showing extensive fibrosis with an increased number of fibroblasts, neovascularization, a sparse lymphocytic infiltrate, but no residual BCC. (D-F, Hematoxylin-eosin stain; original magnification ×2.5). Journal of the American Academy of Dermatology 2014 71, 1005-1008DOI: (10.1016/j.jaad.2014.08.001) Copyright © 2014 American Academy of Dermatology, Inc. Terms and Conditions

Fig 2 Genomic analysis of PTCH1 coding exons and sequence traces from SMO exon 4 and 5 of resistant tumor tissue. A, The top panel confirms the absence of a germline mutation in buccal swab. The primary tumor and resistant tumor, panel 2 and 4 respectively, both harbor the same splice site mutation (arrows) and skewed nucleotide (arrowhead) distribution (indicative of loss of heterozygosity). In the responding tissue, a PTCH1 mutation could no longer be identified. B, Top panels represent resistant tumor 1 and lower panels resistant tumor 2. Arrows indicate the mutations in either exon 4 (left panels) for resistant tumor 2 or exon 5 (right panels) for resistant tumor 1. If the mutation is present in 1 tumor, it is not in the other and vice versa. Normal tissue, primary tumor, and responding tumor tissue display similar wild type sequence (not shown). Journal of the American Academy of Dermatology 2014 71, 1005-1008DOI: (10.1016/j.jaad.2014.08.001) Copyright © 2014 American Academy of Dermatology, Inc. Terms and Conditions