Final Diagnosis -- Pulmonary Lymphangiomyomatosis



Pulmonary Lymphangiomyomatosis (PLAM) is a rare disease, characterized by an abnormal proliferation of smooth muscle cells throughout the interstitium of the lung. The process can also involve extrapulmonary sites such as lymphatics or lymph nodes in the thorax and abdomen (1).

PLAM occurs almost exclusively in women during the reproductive years of life. Although, pediatric cases have been identified (2), as well as cases in older women (3). Patients usually present with progressive dyspnea, chylous effusion (4), hemoptysis and less commonly, massive pulmonary hemorrhage can occur (5). Pulmonary function tests usually show a combined restrictive-obstructive pattern with decreased diffusing capacity and normal or increased total lung volume (5,6,7). Radiographically normal sized or enlarged lungs show diffuse interstitial infiltrates (5,8).

In spite of the characteristic clinical and radiological features of the disease, the definitive diagnosis is usually based on open or transbronchial lung biopsies, although, these procedures can be extremely difficult (5,9,10). In advanced cases of PLAM, open lung biopsy or even transbronchial lung biopsies are frequently avoided due to the severe cardiopulmonary dysfunction that may supervene (11,12), as unfortunately happened in this case. In order to avoid these complications, there is the option of laparotomy in cases in which abdominal CT scan shows a retroperitoneal component. Laparotomy with biopsy of the enlarged lymph nodes can confirm the diagnosis (11). The second problem in making the diagnosis of PLAM is the diagnostic difficulty that a transbronchial or open lung biopsy might possess due to compression and artifacts, secondary inflammatory changes and the small amount of tissue available that make it difficult to recognize the subtle interstitial proliferation of smooth muscle cells, and their differentiation from normal tissue. The recent demonstration of HMB-45 immuno-reactive smooth muscle cells in PLAM cases helps in the differential diagnosis (13). The expression of HMB-45 in an intermingled population of smooth muscle cells is distinct and specific feature. It heps during the evaluation of small biopsies. Its presence in the affected lymph nodes is of paramount importance to make the diagnosis of lymphangiomyomatosis in a lymph node biopsy. PLAM can present a somewhat confusing histological pattern due to the associated intestitial inflammation. If some degree of abnormal smooth muscle proliferation is appreciated or if the clinical history is suggestive of PLAM, immunohstichemical studies including HMB-45 and possibly ERICA and PRICA can be useful in establishing the diagnosis of this rare disorder.

There is no explanation for the immunoreactivity of the population of PLAM cells with HMB-45 (13). This is a mouse monoclonal antibody generated by immunization with pigmented melanoma cell line Mel-1 derived from a lymph node involved by metastatic melanoma (14), which reacts with the large majority of primary and metastatic melanomas and some nevi with high sensitivity and specificity (14,15). HMB-45 also immunoreacts with pigmented neuroectodermal tumors of infancy (16) as well as with smooth muscle cells of angiomyolipomas (17,18,19,20). The common immunohistochemical expression of HMB-45 by angiomyolipomas and PLAM suggests that both have a neuroectodermal origin (21).

The classical stigmata of tuberous sclerosis complex were absent in this case, a condition often associated with PLAM (22,3,21). Cases without this association may be regard as a "forme fruste" of tuberous sclerosis or as an independent disease (21). The clinical course in PLAM usually is that of inexorable pulmonary failure, although prolonged survival with little or no progression of the disease has also been described (23). Variable response has been reported with several types of hormonal therapy including Tamoxifen, oophorectomy and Progesterone-derivatives (24,25,26,27). Since Estrogen receptors were detected in this case, Tamoxifen citrate was initiated. Although, there was no time to see any response to this controversial form of therapy, since the patient die two days after the lung biopsy. Heart-lung transplantation has been another successful procedure in patients with end stage disease (28).


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