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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 .