Division of Oral Diagnostics and Rehabilitation, Department of Dental Medicine, Karolinska Institutet, Stockholm, Sweden.
Department of Oral Pathology, Faculty of Odontology, Malmö University, Malmö, Sweden.
Biol Blood Marrow Transplant. 2020 Oct;26(10):1971-1979. doi: 10.1016/j.bbmt.2020.06.031. Epub 2020 Jul 10.
Graft-versus-host disease (GVHD) can manifest as acute or chronic complications in patients after hematopoietic cell transplantation (HCT). Oral chronic GVHD (cGVHD) occurs in approximately 70% of HCT recipients and includes lichenoid-like mucosal reactions, restricted mouth opening, and salivary gland dysfunction. However, the underlying histopathological presentation remains to be validated in large cohorts. We characterized the histopathological features of oral mucosal cGVHD and devised a scoring model in a large patient cohort (n = 112). Oral mucosal biopsy sections (n = 303) with and without oral cGVHD were identified from archived and current HCT recipients with additional healthy controls. Histological screening was performed on hematoxylin and eosin-stained and periodic acid-Schiff-stained sections. A points-based grading tool (0 to 19, grade 0 to IV) was established based on intraepithelial lymphocytes and band-like inflammatory infiltrate, atrophic epithelium with basal cell liquefaction degeneration, including apoptosis, as well as separation of epithelium and pseudo-rete ridges. Validation involved 62 biopsy specimens, including post-HCT (n = 47) and healthy (n = 15) specimens. Remaining biopsy specimens (n = 199) were blindly graded by 3 observers. Histological severity was correlated with clinical diagnostic and distinctive features, demonstrating a spectrum of individual patient severity, including frequent signs of subclinical GVHD in healthy mucosa. However, oral cGVHD presented with significantly higher (P < .001) scores compared with HCT controls, with moderate to high positive likelihood ratios for inflammatory infiltrate, exocytosis, and basal membrane alterations. The grade II-IV biopsy specimens demonstrated a histopathological diagnosis of active mucosal lichenoid-like cGVHD, highlighting the importance of correlating clinical presentation with the dynamic histopathological processes for improved patient stratification. In addition, this tool could be used for assessing treatments, pathological processes, and immune cellular content to provide further insight into this debilitating disease.
移植物抗宿主病（GVHD）可在造血细胞移植（HCT）后表现为急性或慢性并发症。口腔慢性 GVHD（cGVHD）发生在大约 70%的 HCT 受者中，包括苔藓样黏膜反应、张口受限和唾液腺功能障碍。然而，其潜在的组织病理学表现仍需要在大样本队列中进行验证。我们在一个大的患者队列（n=112）中描述了口腔黏膜 cGVHD 的组织病理学特征，并设计了一个评分模型。从存档和当前的 HCT 受者中确定了有和没有口腔 cGVHD 的口腔黏膜活检切片（n=303），并增加了健康对照者。对苏木精和伊红染色以及过碘酸-雪夫染色的切片进行了组织学筛查。基于上皮内淋巴细胞和带状炎症浸润、萎缩性上皮伴基底细胞液化变性，包括凋亡，以及上皮与假 rete 嵴分离，建立了基于积分的分级工具（0 至 19 分，0 至 4 级）。验证涉及 62 个活检标本，包括 HCT 后（n=47）和健康（n=15）标本。其余活检标本（n=199）由 3 位观察者进行盲法分级。组织学严重程度与临床诊断和特征性表现相关，显示了个体患者严重程度的谱，包括健康黏膜中经常出现的亚临床 GVHD 迹象。然而，与 HCT 对照相比，口腔 cGVHD 的评分显著更高（P<0.001），炎症浸润、外溢和基底膜改变的中至高度阳性似然比。Ⅱ-Ⅳ级活检标本表现为活跃的黏膜苔藓样 cGVHD 的组织病理学诊断，突出了将临床表现与动态组织病理学过程相关联以改善患者分层的重要性。此外，该工具可用于评估治疗、病理过程和免疫细胞含量，以提供对这种使人衰弱的疾病的进一步了解。
