Recurrent lymphangioleiomyomatosis in a lung allograft with COVID-19: autopsy case report and literature review

Abstract

Lymphangioleiomyomatosis (LAM) is a rare neoplastic disease of the lung with a characteristic feature of diffuse cystic changes in bilateral lungs. Lung transplantation is considered to be one of the effective treatments in end stage disease. Patients with LAM who underwent lung transplant tend to have more favorable outcome compared to other end stage lung diseases. We report a case of a female patient who was diagnosed with LAM and received bilateral lung transplantation at 45 years of age. Subsequent allograft biopsies were significant for mild acute cellular rejection (Grade A2), for which the immunosuppressive regimen was adjusted accordingly. At 7 years post-transplant, she presented with shortness of breath, cough, and fatigue, and diagnosed with a viral infection. Her chest imaging was unremarkable. However, a transbronchial biopsy was performed to rule out rejection and revealed foci of spindle cells proliferation, with positive HMB-45 and smooth muscle actin immunohistochemical studies, confirming the diagnosis of recurrent LAM. After she was discharged, she was re-admitted 1 week later with severe COVID-19. Her clinical course was complicated by acute respiratory distress syndrome, respiratory failure, and gastrointestinal hemorrhage. The patient passed away on day 36 of hospital stay. Autopsy was requested and confirmed the pathology of recurrent LAM and diffuse alveolar damage from COVID-19.

Pulmonary lymphangioleiomyomatosis (LAM): A literature overview and case report

“…Currently, although receiving no specific treatment, our patient is leading a normal life. This observation is consistent with the literature and case reports [4] . LAM can stabilize and regress spontaneously over a certain amount of time; this might explain why LAM is slow to diagnose and often creates diagnostic confusion at primary health care levels.…”

“…Compared with our case, the age of detection was earlier (36 years old), and the patient had only had 2 prior episodes of pneumothorax before LAM was diagnosed. Immunohistochemical staining showing HMB-45-positive LAM cells was also used in our case to obtain a definitive diagnosis [4] .…”

“…Other microorganisms that can cause pulmonary cysts include Staphylococcus species, Coccidioides species, and parasitic infections caused by the lung fluke Paragonimus westermani. Birt-Hogg-Dubé syndrome (BHD) can also mimic pulmonary LAM, with a similar clinical presentation of young women with recurrent pneumothorax; however, the cysts in BHD are surrounded by normal lung parenchyma without evidence of proliferative cancer cell populations or significant inflammation [4] .…”

“…The proliferation of LAM cells in the lymphatic system can lead to enlarged lymph nodes in hilar, mediastinal, and extrathoracic regions, sometimes dilating lymphatic vessels in the lungs and thoracic duct and leading to chylous pleural or abdominal effusion. The proliferation of LAM cells in pulmonary veins can cause venous obstruction and lead to pulmonary hypertension, which can present as hemoptysis [1] , [2] , [3] , [4] , [5] .…”

Lymphangioleiomyomatosis: A Literature Overview

“…LAM occurs more often in patients with S-LAM, and patients with S-LAM can be caused by mutations in the TSC2 gene. 4 Mutations in these genes result in dysregulation of the mammalian target of the mTOR pathway of rapamycin 5 .…”