Lymphangioleiomyomatosis, LAM

Lymphangioleiomyomatosis is a diffuse pulmonary infiltrate of short spindle cells, usually in association with cystic changes, occurring in women of reproductive age. LAM may also arise within lymph nodes, mediastinum, retroperitoneum and pelvis. Recent studies have demonstrated that LAM is a neoplasm arising from constitutive activation of the mammalian target of rapamycin signalling pathway dysregulated by a functional loss of tuberous sclerosis complex genes. It has also been suggested that the pulmonary lesions represent metastases from primary uterine lesions4.

Epidemiology

This is rare condition. It most often occurs sporadically, but some cases are associated with tuberous sclerosis complex (TSC). 25-40% of women with TSC develop LAM. Renal angiomyolipomas occur in most women with TSC and in about half of the cases of sporadic LAM.

Clinical features

Patients show a slow progression to respiratory failure.

Histopathology

Lungs show widespread nodules composed of myoid cells, associated with dilated lymphatics and cystic change. The myoid cells have variably clear cytoplasm.

Immunohistochemistry

HMB-45	5/61
Melan-A	positive
Mitf	1/61
tyrosinase	0/61

Lymphangioleiomyomatosis may recur after lung transplantation: the recurrent LAM lesions are composed of recipient cells2.

Prognosis

Without transplantation, the median survival is 8 to 10 years3.

References

1 Miettinen M et al. Microphthalmia transcription factor in the immunohistochemical diagnosis of metastatic melanoma: comparison with four other melanoma markers. Am J Surg Pathol 2001;25:205-211.

2 Bittmann I et al. Recurrence of lymphangioleiomyomatosis after single lung transplantation: new insights into pathogenesis. Human Pathol 2003;34:95-98.

3 Hornick JL,Fletcher CD. PEComa: what do we know so far? Histopathology 2006; 48:75-82

4 Hayashi T, Kumasaka T, Mitani K, Terao Y, Watanabe M, Oide T, et al. Prevalence of uterine and adnexal involvement in pulmonary lymphangioleiomyomatosis: a clinicopathologic study of 10 patients. Am J Surg Pathol. 2011 Dec;35(12):1776-85.

This page last revised 6.3.2012.