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Advances in dermatology and venereology Acta Dermato-Venereologica
Testicular Cancer in Monozygotic Twin Brothers with Urticaria Pigmentosa
Tatiana PÉČOVÁ 1, Karolína VORČÁKOVÁ 1, Markéta ŽALIOVÁ 2, Tatiana BURJANIVOVÁ 3, 4, Bibiana MALICHEROVÁ 3, 4, Lukáš PLANK 5, Jan TRKA 2, Klaudia PÉČOVÁ 1, Katarína ADAMICOVÁ 5, Martin PÉČ 6 and Juraj PÉČ 1 * Departments of 1 Dermato-Venereology, 5 Pathology and 6 Medical Biology, Jessenius Faculty of Medicine in Martin, Comenius University in Bratislava, Kollarova 2, 036 01 Martin, Slovakia, 2 Childhood Leukaemia Investigation Prague( CLIP), Department of Paediatric Haematology and Oncology, 2 nd Faculty of Medicine, Charles University and University Hospital Motol, Prague, Czech Republic, Commenius University in Bratislava, Jessenius Faculty of Medicine in Martin, Biomedical Center Martin( JFM CU), 3 Department of Molecular Biology and 4 Division of Oncology JFM CU, Martin Slovakia. E-mail: jpec @ jfmed. uniba. sk Accepted Dec 6, 2017; Epub ahead of print Dec 12, 2017
Urticaria pigmentosa( UP) is the most common variant of cutaneous mastocytosis. The occurrence of UP in twins is rare. We have described a case of monozygotic twin brothers, with the first signs of UP at the age of 4 months( 1) and now present the development of their disease until 43 years of age, with the additional appearence of testicular cancer at age 30.
CASE REPORT
The UP lesions in both twins – diffuse macules affecting the whole body( Fig. 1), except the face – remained clinically unchanged during the 43 years of life apart from the short period of chemotherapy in one of the twins. In 2003, left orchiectomy was performed on one twin due to palpable testicular tumour, and in 2004, right orchiectomy was performed on the other due to the same reason. In both brothers the histology confirmed mixed germ cell tumour with the dominant component of embryonal carcinoma( more than 90 % of the tumour) with a minor level of a yolk sac component and choriocarcinoma. Both twins were treated with 4 cycles of chemotherapy in monthly intervals( bleomycin, etoposide, cisplatine), and so far no recurrence of the tumour has been observed. In one twin, the UP lesions temporarily disappeared after the first cycle of chemotherapy, and reappeared after the last session, whereas in the second twin the UP lesions remained stable during the chemotherapy.
In both brothers, all routine biochemical parameters were within normal levels. The serum tryptase levels, 13.1 and 16.8 ng / ml, were both within reference values( below 20 ng / ml for adults – ImmunoCAP Tryptase test). The abdominal ultrasonography and chest X-ray were without any pathology.
The skin biopsy from both brothers had identical histological features of UP with an intact epidermis and a pleomorphic, mainly granulated mast cells with positive chloroacetate esterase, and CD117 – proto-oncogene c-kit in the upper corium. The bone
Fig. 1. The brothers’ skin phenotypes at the age of 16 years( a) and 43 years( b), respectively.
marrow trepanobiopsy in both brothers showed proportional representation of precursors of all 3 lines of hematopoiesis, the presence of trilinear maturation without proliferation of blasts with the presence of rare, dispersedly situated granulated mast cells( CD117 +, CD25 –), without infiltration of mast cell populations, whereas the skeletal scintigraphy was negative( with Tc-MDP methylene diphosphonate as imaging agent).
Whole blood samples and saliva were collected from the twins. DNA was isolated by using DNeasy Blood and Tissue Kit( Qiagen). First we worked with DNA isolated from the whole blood, where Sanger sequencing of the entire coding region of the proto-oncogene KIT was performed( 2). Since Sanger sequencing of c-kit gene did not reveal any pathogenic mutation, we decided to analyse the whole exome, where we found D816V of the KIT gene in both samples. However, the mutation rate was very low, which is why Sanger sequencing did not reveal any mutation. Assuming that the twins originate from a mosaic embryo, we isolated DNA from the saliva for further examination. Allele-specific PCR( AS-PCR) for the KIT D816V were performed in patients’ saliva samples( 3). We found D816V mutation in both twins( Fig. S1 1).
Sequencing libraries were prepared from DNA using Agilent SureSelectXT HumanAllExon V5 kit according to the manufacturer’ s instructions( Agilent, Technologies, USA). High throughput sequencing( 2x75 cycles) was performed on NextSeq500 using High Output Kit( Illumina, USA). Read pairs were aligned to the human genome reference( hg19) using Burrows-Wheeler aligner and futher processed by Picard tools http:// broadinstitute. github. io / picard /)( 4). Variant calling was performed using VarScan( 5). Regions of interest were visually inspected in Integrative Genomics Viewer( IGV)( 6). Part of the exone 17( Chr4: 55599271-55599370; hg19) of the KIT gene( NM _ 000222) surrounding codon D816 was amplified by singleround PCR using primer pairs listed in Table SI 1.
1 https:// www. medicaljournals. se / acta / content / abstract / 10.2340 / 00015555-2861 doi: 10.2340 / 00015555-2861 Acta Derm Venereol 2018; 98: 528 – 529
This is an open access article under the CC BY-NC license. www. medicaljournals. se / acta Journal Compilation © 2018 Acta Dermato-Venereologica.