Incidence, Histopathological Features and Differential Diagnosis of Cutaneous Graft Versus Host Disease in Allogeneic Bone Marrow Transplantation

Objectives: Hematopoietic stem cell transplantation by allogeneic bone marrow transplantation is a method used in the treatment of various genetic, immunological disorders, hematologic and solid organ malignancies. Graft versus Host Disease is one of the major and fatal complications of allogeneic bone marrow transplantation. It is a systemic disease affecting five main areas: skin, gastrointestinal tract, liver, lung and hematopoietic system. Diagnosis of cutaneous Graft versus Host Disease is made by the correlation between clinical and histopathological findings of the patient. The present study aims to investigate the incidence of cutaneous graft versus Host Disease in allogeneic bone marrow transplantation patients in our center, to discuss the histopathological features and differential diagnosis of cutaneous graft versus Host Disease in the light of the literature.
Methods: The pathology slides of allogeneic bone marrow transplantation patients who were diagnosed as graft versus Host Disease in our pathology department between January 2015 and January 2019 were re-evaluated. Epidermal and dermal histomorphological findings of the disease were classified; the patients’ clinical and demographic information was obtained from the files. The incidence of cutaneous Graft versusHost Disease was calculated.
Results: In our center, between January 2015 and January 2019, 273 pediatric and 100 adult patients underwent allogeneic and 181 autologous bone marrow transplantation. Twenty-three patients who underwent allogeneic bone marrow transplantation had cutaneous Graft versus Host Disease whereas and 21 patients had gastrointestinal Graft versus Host Disease. The incidence of cutaneous and gastrointestinal Graft versus Host Disease was 16.1% whereas the incidence of cutaneous Graft versus Host Disease was 8.42%. The most common clinical differential diagnosis of cutaneous Graft versus Host Disease was drug reaction (74%). The most common epidermal histomorphologic finding in our cases was keratinocyte necrosis (87%). In our cases, the most common epidermal histomorphologic finding was keratinocyte necrosis (87%). This was followed by vacuolar degeneration in basal keratinocytes (63%), acanthosis and spongiosis (61%), respectively. The most common finding in the dermis was pigment incontinence (59%). Of the patients with Graft versus Host Disease, 56% had transplantation from unrelated donors, whereas 44% of them had transplantation from their relatives.
Conclusion: Cutaneous Graft versus Host Disease is a common complication of allogeneic hematopoietic stem cell transplantation. It is associated with high mortality rates and has a significant negative impact on the patient's quality of life. Dermatological early recognition of the disease; histopathological evaluation and verification with differential diagnosis plays a key role in preventing patient morbidity and mortality.

Allojenik Kemik Ýliði Transplantasyonu Yapýlan Hastalarda Kutanöz Graft Versus Host Hastalýðýnýn Görülme Oraný, Histopatolojik Özellikleri ve Ayýrýcý Tanýlarý

Amaç: Allojenik kemik iliði transplantasyonu ile hematopoetik kök hücre aktarýmý, çeþitli genetik, immünolojik bozuklukta, hematolojik ve solid organ malignitelerinin tedavisinde kullanýlan bir yöntemdir. Graft versus host hastalýðý allojenik kemik iliði transplantasyonunun temel ve ölümcül komplikasyonlarýndan biridir. Deri, gastrointestinal trakt, karaciðer, akciðer ve hematopoetik sistem olmak üzere beþ ana bölgeyi etkileyen sistemik bir hastalýktýr. Kutanöz Graft Versus Host Hastalýðýnýn tanýsý hastanýn klinik bulgularý ile histopatolojik bulgularýnýn korelasyonu ile konulur. Çalýþmamýzýn amacý, merkezimizde allojenik kemik iliði transplantasyonu yapýlmýþ hastalarda kutanöz graft versus host hastalýðýnýn görülme oranýný belirlemek, hastalýðýn histopatolojik özelliklerini ve ayýrýcý tanýsýný literatür eþliðinde tartýþmaktýr.
Gereç ve yöntemler: Kurumumuzda Ocak 2015 - Ocak 2019 tarihleri arasýnda allojenik kemik iliði transplantasyonu yapýlmýþ ve patoloji anabilim dalýmýzda graft versus host hastalýðý tanýsýný almýþ olan Hastalara ait deri biyopsi preparatlarý yeniden deðerlendirilip epidermal ve dermal histomorfolojik bulgular sýnýflandýrýldý. Hastalarýn klinik ve demografik bilgilerine dosyalarýndan ulaþýldý. Kutanöz Graft Versus Host hastalýðý görülme oraný belirlendi.
Bulgular: Merkezimizde Ocak 2015- Ocak 2019 tarihleri arasýnda pediatrik 173, eriþkin 100 olmak üzere toplam 273 hastaya allojenik, 181 hastaya ise otolog kemik iliði transplantasyonu yapýldý. Allojenik kemik iliði transplantasyonu yapýlan hastalarýn 23’inde kutanöz, 21’inde ise gastrointestinal Graft Versus Host hastalýðý görüldü. Kutanöz ve gastrointestinal Graft Versus Host hastalýðý görülme oraný %16,1; yalnýzca kutanöz Graft Versus Host hastalýðý görülme oraný ise %8,42 idi. Kutanöz Graft Versus Host hastalýðý’nýn klinik ön tanýlarý arasýnda en sýk ilaç reaksiyonu yer almakta idi (%74). Preparatlarda en sýk görülen epidermal histomorfolojik bulgu keratinosit nekrozu idi (%87). Bunu sýrasý ile bazal keratinositlerde vakuoler dejenerasyon (%63) ve Achanthosis ve spongiyoz (%61) izlemekte idi. Dermiste en sýk görülen bulgu ise Pigment incontinence idi (%59). Graft Versus Host hastalýðý saptanan hastalarýn %56’sýna akraba olmayan, %44’üne ise akraba olan donörlerden transplantasyon yapýlmýþtý.
Sonuç: Kutanöz Graft Versus Host Hastalýðý allojenik hematopoietik kök hücre transplantasyonunun sýk görülen bir komplikasyonudur. Yüksek mortalite oranlarý ile iliþkilidir ve hastanýn yaþam kalitesi üzerine belirgin negatif etkisi olan bir hastalýktýr. Dermatolojik olarak hastalýðýn erken tanýnmasý; ayýrýcý tanýlarý ile birlikte histopatolojik olarak deðerlendirilmesi ve verifikasyonu hasta morbidite ve mortalitesinin önlenmesinde kilit rol oynar. (SETB-2019-09-118)