Only 21 cases of women with tuberous sclerosis complex (TSC) and lymphangioleiomyomatosis (LAM) are known to the LAM registry at the National Institutes of Health. Of these cases, only two are in African American women (1). Due to the small number of diagnosed cases, there are limited published data estimating the true incidence or prevalence of the disease. Review of literature revealed no further data regarding racial distribution.
The patient is a 35-year-old African American female who presented with complaints of progressively worsening dyspnea and back pain for several weeks. There is no family history of TSC. Remarkable physical findings included fibrous papules on face and neck. An initial radiograph revealed a pneumothorax involving 50% of right hemithorax. Blood chemistries and blood counts revealed no abnormalities. Urinalysis showed hematuria but no signs of infection. CAT scan of chest, abdomen and pelvis was performed. Multiple intraparenchymal lung cysts and bilateral renal masses were noted. The patient underwent thoracoscopic surgery with mechanical pleurodesis. Lung and renal biopsies were performed. The right lung was completely re-expanded. The patient had an uneventful post-operative course and was discharged home in stable condition.Lung biopsy was consistent with LAM with bronchoalveolar cell proliferation as interpreted by the LAM Clinical Center at NIH. Immunochemical stains revealed LAM cells to be positive for smooth muscle actin and negative for HMB-45. The renal biopsy was consistent with angiomyolipoma.DISCUSSION: Sporadic lymphangioleiomyomatosis (S-LAM) is a non-inheritable disease characterized by peribroncho-vascular, and perilymphatic proliferation of smooth muscle with loss of lung parenchyma leading to cystic lesions. S-LAM occurs exclusively in women of childbearing age. There are about 400 cases in the US. The radiographic appearance of LAM can range from normal chest radiograph (early in the disease) to interstitial opacities, honeycomb changes, and hyperinflation.TSC is sporadic or inherited as an autosomal dominant syndrome characterized by hamartomas of skin, eyes, kidney and central nervous system. It is caused by mutations of tumor suppressor genes TSC1 (9q34.3) and TSC2 (16p13.3). There are an estimated 20-25,000 women with TSC in the US. Lung involvement in TSC can be cystic (LAM) or nodular or both. The LAM in many cases of TSC may be asymptomatic and therefore undetected (1). TSC-LAM and S-LAM are clinically, histologically, and radiographically similar in nature.TSC patients with symptomatic LAM present with dyspnea. Onset of disease may be heralded by a spontaneous pneumothorax, which occurs in approximately one-third of patients. It is characterized pathologically by the proliferation of atypical pulmonary interstitial smooth muscle and by cystic changes. Recent research has demonstrated that abnormalities in synthesis of catecholamines may play a part in the pathophysiology of the disease.Symptomatic TSC-LAM carries a poor prognosis, with progressive disease being common. No effective treatment has been found. However, treatment with progesterone, luteinizing hormone-releasing hormone analogs, and/or oophorectomy is recommended. Lung transplantation may be an option for some patients. Death occurs secondary to respiratory insufficiency, often within five years of the onset of symptoms.
This is a case of symptomatic LAM in an African American woman with TSC. In data published by the NIH, only 6% of diagnosed TSC-LAM cases are African American. TSC-LAM is either a very rare disorder among African American women or it has been under-diagnosed. Aggressive efforts at case finding would provide a more accurate assessment of racial distribution and opportunity for early detection and transplant referral for this fatal disease.
R.K. Gill, None.