Clinical History
A 65 year old female patient with tuberous sclerosis (TS).
Imaging Findings
A few selected trans-axial computed tomography (CT) images of the chest show multiple randomly-distributed and variably-sized ground-glass nodular opacities. The nodules do not exceed 1cm in size. The abnormality is seen throughout both lungs; however, a slight upper lobar and peripheral predominance is noted. No cystic changes, lymphadenopathy, pleural effusions or pneumothoraces seen. The findings were stable over more than three years of imaging follow-up.
Discussion
Although cystic changes of lymphangioleiomyomatosis (LAM) is typically the first consideration when facing a chest image of a tuberous sclerosis (TS) patient, it is not the only imaging manifestation that could be encountered in that clinical sitting. The entity of multifocal micronodular pneumocyte hyperplasia (MMPH) is another interesting abnormality that usually occurs in TS patients.
On histological evaluation of MMPH, multicentric nodular hyparplastic changes of type 2 pneumocytes are seen with variable degrees of cellular atypia. The alveolar septa show fibrous thickening and the alveolar spaces are infiltrated by macrophages. No smooth muscle proliferation is seen, in contrast to LAM. In addition, oestrogen receptors, progesterone receptors and HMB-45 smooth muscle staining is negative. In contrast to atypical adenomatous hyperplasia (AAH), the nuclear-to-cytoplasmic ratio is not high, the degree of macrophages infiltration is more pronounced and no CEA or p53 immunoreactivity is seen.
MMPH occurs in both the TS and LAM populations. However, it is more commonly seen in the former group. The awareness of this entity is increasing due to the increased number of CT examination obtained in such patients. This entity is believed now to be far more common that what was previously reported. In fact, an incidence as high as 28-43% has been documented in TS patients. In addition, a few proven cases of MMPH in non-TS and non-LAM patients have been reported.
The entity of MMPH is usually asymptomatic. The discovery of the abnormality is usually made on chest radiographs or CT studies performed for LAM- or TS-related presentations. A few cases primarily presenting with mild dyspnoea, cough or mild hypoxemia have been reported. One case of mortality has also been documented.
The chest radiograph is usually normal, but small nodular scattered opacities could be seen. CT images show a typical appearance of randomly-distributed 1-8mm ground-glass nodules. The distribution is usually diffuse, but a slight upper lobar and peripheral predominance has been seen. The findings may or may not be associated with parenchymal cysts of LAM.
MMPH is a benign entity with no known malignant potential. The MMPH imaging findings do not show progression over time. No treatment is usually needed in such cases. It is important to recognize this entity, especially when facing TS or LAM patients. Confusion with other more sinister diseases such as AAH or multicentric bronchoalveolar carcinoma should be avoided. In non-TS or non-LAM patients, this distinction might be difficult. In theses instances, trans-bronchial or video assisted thoracoscopic surgical biopsies might be helpful. Imaging follow-up could also be an alternative way of managing these patients.
Differential Diagnosis List
Multifocal Micronodular Pneumocyte Hyperplasia (MMPH) in Tuberous Sclerosis (TS).
Final Diagnosis
Multifocal Micronodular Pneumocyte Hyperplasia (MMPH) in Tuberous Sclerosis (TS).
