Clinicopathological analysis of multifocal micronodular pneumocyte hyperplasia associated with tuberous sclerosis in Japan

Abstract

(80%) were women and the mean age was 37 years. Three patients had a family history of TSC. The radiological findings were small multiple nodular shadows with ground-glass opacity randomly distributed in the bilateral whole-lung fields in most patients. Differentiation from multiple atypical adenomatous hyperplasia or metastatic lung cancer was necessary in most patients. In 11 patients, the diagnostic method used to identify pulmonary lesions of MMPH with TSC was VAT. Among the complications of MMPH with TSC, lymphangioleiomyomatosis was recognized in 53% of patients. The prognosis was comparatively good because only one patient died of respiratory failure. The histological findings were papillary or tubular proliferation of type II pneumocytes without nuclear atypia lining the thickened alveolar septa and lymphocyte infiltration. Immunohistochemical staining for cytokeratin, and surfactant proteins A and B was positive in alveolar lining cells of all MMPH lesions. However, staining for HMB-45, a-smooth muscle actin, p53, carcinoembryonic antigen and hormonal receptor was negative in most patients. Conclusions: Surgical investigation and immunohistochemical staining for pathological markers are useful for diagnosing MMPH when the radiological findings indicate multiple micronodules with ground-glass opacity in patients with TSC.

Tuberous Sclerosis Complex Diagnostic Criteria Update: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference

“…These lesions stain with cytokeratin and surfactant proteins A and B, but not with HMB-45, alpha smooth muscle actin, or hormonal receptors. 55 MMPH does not have known prognostic or physiologic consequences, although there have been at least two reports of respiratory failure associated with MMPH. 55,56 The precise prevalence of MMPH in patients with TSC is not known, but may be as high as 40–58%.…”

“…55 MMPH does not have known prognostic or physiologic consequences, although there have been at least two reports of respiratory failure associated with MMPH. 55,56 The precise prevalence of MMPH in patients with TSC is not known, but may be as high as 40–58%. 57,58 There is no gender restriction and MMPH may occur in the presence or absence of LAM in patients with TSC.…”

Clinical Course of Histologically Proven Multifocal Micronodular Pneumocyte Hyperplasia in Tuberous Sclerosis Complex: A Case Series and Comparison with Lymphangiomyomatosis

“…Previous reports described only 2 patients who may have died from respiratory failure, possibly due to MMPH deterioration [15, 16]. Generally, the prognoses in most previously reported cases of MMPH seemed fair [4, 5]. In our case series, all 9 patients, even the 19-year-old patient, had not deteriorated at follow-up when clinical findings, radiographic findings, pulmonary function test results, and serum biomarkers were assessed.…”

“…Histological examination typically reveals multicentric, well-demarcated, nodular type II pneumocystic growth [1, 2]. In contrast with lymphangioleiomyomatosis (LAM), which is a more common lung manifestation in patients with TSC [3], MMPH is less progressive [4, 5]. However, because of its rarity, no previous study has described the detailed clinical course of the disease, such as changes in radiographic findings and pulmonary function.…”

Reversed Halo Sign in Tuberous Sclerosis Complex

“…Typical radiological features of MMPH are multiple tiny nodules that are diffusely and randomly scattered throughout the lung [3, 4]. Kobashi et al noted that computed tomography (CT) identified ground-glass opacity (GGO) in all of the 15 patients with MMPH [5]. On the other hand, Muzykewicz et al described that 67% of TSC patients with multiple nodules had both solid and ground-glass nodules.…”