Treichel Alison M, Boeszoermenyi Barbara, Lee Chyi-Chia Richard, Moss Joel, Kwiatkowski David J, Darling Thomas N
Department of Dermatology, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio, USA.
Cancer Genetics Laboratory, Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
JID Innov. 2023 Jan 9;3(2):100180. doi: 10.1016/j.xjidi.2023.100180. eCollection 2023 Mar.
Skin findings can be critical to determining whether a patient with lymphangioleiomyomatosis (LAM), a progressive pulmonary disease that predominantly affects adult women, has sporadic LAM or LAM in association with tuberous sclerosis complex (TSC). Three individuals with LAM underwent evaluation for TSC-associated mucocutaneous and internal findings. We used our previously published algorithm to confirm the clinical suspicion for mosaicism and guide the selection of tissue specimens and genetic workup. Next-generation sequencing of cutaneous findings was used to confirm clinical suspicion for mosaic TSC in individuals with LAM. Two individuals previously thought to have sporadic LAM were diagnosed with mosaic TSC-associated LAM upon next-generation sequencing of unilateral angiofibromas in one and an unusual cutaneous hamartoma in the other. A third individual, diagnosed with TSC in childhood, was found to have a mosaic pathogenic variant in in cutaneous tissue from a digit with macrodactyly. Accurate diagnosis of mosaic TSC-associated LAM may require enhanced genetic testing and is important because of the implications regarding surveillance, prognosis, and risk of transmission to offspring.
皮肤表现对于确定患有淋巴管平滑肌瘤病（LAM）的患者是散发性LAM还是与结节性硬化症（TSC）相关的LAM至关重要，LAM是一种主要影响成年女性的进行性肺部疾病。三名LAM患者接受了TSC相关的皮肤和内部表现评估。我们使用之前发表的算法来确认对嵌合体的临床怀疑，并指导组织标本的选择和基因检查。对皮肤表现进行二代测序，以确认LAM患者中存在镶嵌型TSC的临床怀疑。两名之前被认为患有散发性LAM的患者，在对其中一人的单侧血管纤维瘤和另一人的一种不寻常的皮肤错构瘤进行二代测序后，被诊断为镶嵌型TSC相关的LAM。第三名个体在儿童期被诊断为TSC，在其患有巨指症的手指皮肤组织中发现了镶嵌型致病变体。准确诊断镶嵌型TSC相关的LAM可能需要加强基因检测，这很重要，因为它关系到监测、预后以及遗传给后代的风险。
