Muir T E, Leslie K O, Popper H, Kitaichi M, Gagné E, Emelin J K, Vinters H V, Colby T V
Department of Pathology, Mayo Clinic, Rochester, Minnesota, USA.
Am J Surg Pathol. 1998 Apr;22(4):465-72. doi: 10.1097/00000478-199804000-00012.
Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder characterized by mental retardation, seizures, and central nervous system and visceral hamartomas. Pulmonary involvement manifesting as lymphangioleiomyomatosis (LAM) occurs in 1% of patients (all women) with TSC. Micronodular pneumocyte hyperplasia also has been described as a rare pulmonary manifestation of TSC. We report 14 patients with micronodular pneumocyte hyperplasia (MNPH). The patients ranged in age from 23 to 57 years (mean 37.5). There were 12 women and 2 men. Nine of the patients (one man and eight women) had documented clinical manifestations of TSC: seven with LAM, two without LAM (including one man). Of the five patients who did not have TSC, three had LAM and two did not (including one man). Histologically, all 14 cases demonstrated multiple well-demarcated nodules usually measuring up to 8 mm in size, but most were 1-3 mm. The nodules were produced by a proliferation of enlarged cytologically benign type II pneumocytes, with an associated increase in alveolar macrophages and interstitial reticulin. Immunoperoxidase studies showed the type II pneumocytes within lesions to be reactive with antibodies to cytokeratin (four of four), epithelial membrane antigen (EMA) (five of five), and surfactant apoprotein B (8 of 10). HMB-45 was negative in the MNPH lesions in all nine cases studied. Follow-up was available in 9 of 10 living patients and ranged from 1 to 14 years (mean 6 years). Nine patients are alive; six are clinically stable and three have repeated pneumothoraces related to LAM. Four patients have died. None of the deaths were attributable to MNPH. MNPH appears to be a hamartomatous proliferation occurring most frequently in patients with tuberous sclerosis, is separable from and not a manifestation of LAM, has been observed to occur in men, and, like other hamartomas of tuberous sclerosis, does not appear to possess malignant potential.
结节性硬化症（TSC）是一种常染色体显性疾病，其特征为智力迟钝、癫痫发作以及中枢神经系统和内脏错构瘤。肺部受累表现为淋巴管平滑肌瘤病（LAM），见于1%的TSC患者（均为女性）。微小结节性肺细胞增生也被描述为TSC罕见的肺部表现。我们报告了14例微小结节性肺细胞增生（MNPH）患者。患者年龄在23至57岁之间（平均37.5岁）。其中有12名女性和2名男性。9例患者（1名男性和8名女性）有记录在案的TSC临床表现：7例患有LAM，2例无LAM（包括1名男性）。在5例无TSC的患者中，3例患有LAM，2例无LAM（包括1名男性）。组织学上，所有14例均显示多个边界清晰的结节，大小通常达8mm，但多数为1 - 3mm。这些结节由细胞学上良性的增大的II型肺细胞增殖形成，伴有肺泡巨噬细胞和间质网状纤维增加。免疫过氧化物酶研究显示，病变内的II型肺细胞对细胞角蛋白抗体（4/4）、上皮膜抗原（EMA）抗体（5/5）和表面活性物质载脂蛋白B抗体（10/8）呈反应性。在所研究的9例病例中，HMB - 45在MNPH病变中均为阴性。10例在世患者中有9例有随访记录，随访时间为1至14年（平均6年）。9例患者存活；6例临床稳定，3例因LAM反复发生气胸。4例患者死亡。无一例死亡归因于MNPH。MNPH似乎是一种错构瘤性增殖，最常发生于结节性硬化症患者，可与LAM区分且不是LAM的表现，已观察到在男性中发生，并且与结节性硬化症的其他错构瘤一样，似乎不具有恶性潜能。
