Lung biopsy with proliferation of placed in fascicles surrounding venous structures (16).

History of Present Illness

Lymphangiomyomatosis Pathophysiology

Swapna Jain, M.D. PGY-3, Brooke Kania OMS-III, Brittanie West, D.O., S. Whitney Courtney, D.O.United Hospital Center Family Medicine Residency, Bridgeport, WV

Hospital Course and Management

Lymphangioleiomyomatosis: A Case Report and Review of Clinical Features and Management

A 39-year-old female presented to the Emergency Department with a chief complaint

of 2 days of sharp, left sided chest pain radiating to her left neck and upper back

associated with shortness of breath and an episode of presyncope. Past medical history

significant for chronic sinusitis and an episode of bronchitis, treated 2 months prior to

her presentation. Family history was insignificant. Patient was a never smoker and

lived a very healthy, active lifestyle. She worked as a sales representative for a

technology company requiring frequent travel across the country.

Physical ExamVitals: Temperature: 36.5 °C (97.7 °F), Heart Rate: 82, BP (Non-Invasive): 115/71,

Respiratory Rate: 20, SpO2: 91% on room air

Constitutional: Appears in respiratory distress

Head: Normocephalic and atraumatic.

Neck: Normal range of motion. No JVD.

Cardiovascular: Normal rate and regular rhythm. No murmur heard.

Pulmonary/Chest: Tachypneic, Lung sounds absent in left lower lobe and decrease

in left upper lobe, lung sounds clear in right lobes

Abdominal: Soft., non-tender, positive bowel sounds

Musculoskeletal: Normal range of motion and strength. No edema on bilateral lower

extremities.

Neurological: She is alert and oriented to person, place, and time.

Skin: Skin is warm and dry. No rash noted. No jaundice.

The patient appeared pale, diaphoretic and in respiratory distress with an oxygen

saturation of 91% on room air upon presentation to the ED. Physical exam was

significant for diffusely diminished lung sounds especially on her left lung fields.

Chest x-ray and CT chest was significant for large left spontaneous

pneumothorax, for which urgent pigtail thoracostomy was performed, and severe

emphysema. She was admitted with a left sided chest tube on nasal cannula oxygen for

further management and workup of her spontaneous pneumothorax and severe

emphysema. Pulmonology and Cardiothoracic Surgery was consulted for assistance in

this case. Workup included a renal ultrasound negative for angiomyolipoma,

negative HIV screen, no alpha-1-antitrypsin deficiency, normal ACE levels, and

absent anti-SSA or anti-SSB antibodies but a mildly positive ANA titer of 1:40.

Patient was unable to be transferred to a higher level of care due to insurance

issues. Thus, the patient opted to proceed with surgical management at the community

hospital. She underwent chemical pleurodesis to prevent further pneumothoraces with

Video-Assisted Thoracoscopic Surgery (VATS) of the left lower lobe with wedge

excision, which was sent to pathology, and pleural tent procedure to prevent air leaks

postoperatively. She was extubated successfully onto nasal cannula oxygen and her

postoperative course was uncomplicated. Pathology showed prominent cystic

structures coated by groups on bland epithelioid to spindle eosinophilic cells, which

were strongly positive for Actin and Progesterone receptors with significant HMB45

and MITF staining. These findings were consistent with lymphangioleiomyomatosis

(LAM).

She was later discharged in stable condition with nasal cannula oxygen and set up

with a LAM specialty clinic. She was started on Sirolimus treatment to decrease the

rate of progression of disease. About 7 months after her discharge, she successfully

underwent bilateral lung transplantation.

LAM occurs due to rapid expansion of smooth muscle cells in the lung parenchyma and

airway walls, as well as the lymphatic system (1). LAM cells morphologically consist of

myofibroblast spindle cells or epithelioid polygonal cells, which proliferate and lead to

alveolar air restriction (2).

Congenital LAM (40%): Typically occur at younger ages, have alterations in tuberous

sclerosis complex genes 1 and 2 (TSC1 and TSC2) (1). TSC1 and TSC2 help regulate

mammalian target of rapamycin (mTOR) signaling pathways (2). Congenital LAM

presents more aggressively affecting the brain, kidney, and integumentary systems, with

less common pulmonary manifestations (7).

Sporadic LAM (60%): Typically occurs later in life with less complications. Patients

may exhibit melanocytic mutation markers on biopsy, which can be specific to

pulmonary LAM. These markers include HMB45 monoclonal antibody and

microphthalmia transcription factor (MiTF), both of which stained positively in our

patient’s biopsy (8, 9).

Lymphangiomyomatosis Diagnostic Features

Patients who experience a spontaneous pneumothorax have higher risk of recurrence and therefore pleurodesis is a viable option to prevent further complications through lung re-

expansion (4, 5). Transplant is recommended for patients with severe alveolar degeneration, when DLCO is < 40% of predicted and VO2max is < 50% of predicted (6). This can be

managed pharmacologically with Sirolimus (immunosuppressant that targets MTOR and interrupts T cell activation downstream of the IL-2 receptor).

LAM typically presents in females of childbearing age with pulmonary manifestations.

Patients who undergo exercise testing may exhibit hypoxemia with poor ventilation

and gas exchange (1). Pulmonary function testing may be significant for a decrease in

forced expiratory volume in 1 second (FEV1) and diffusion capacity for carbon

monoxide (DLCO) (3). Radiographic findings can be notable for hyperinflated lungs

and diffuse thin-walled cysts evident in lung parenchyma (3). Workup includes

diagnosis of exclusion with specific antibodies or titers such as anti-SSA antibodies,

anti-SSB antibodies, ACE levels, alpha-1-antitrypsin levels, and VEG-F antibodies

with definitive diagnosis limited to tissue confirmation.

Imaging and Pathology

A)

B)

Figure 1: Actual CT Chest with IV contrast of our presented patient.

A) and B) Left sided pneumothorax shown with severe emphysema

(1) Taveira-Dasilva, A. M., & Moss, J. (2016). Epidemiology, pathogenesis and diagnosis of lymphangioleiomyomatosis. Expert opinion on orphan drugs, 4(4), 369-378.(2) Krymskaya, V. P. (2008). Smooth muscle–like cells in pulmonary lymphangioleiomyomatosis. Proceedings of the American Thoracic Society, 5(1), 119-126.(3) Taveira-Dasilva, A. M., Steagall, W. K., & Moss, J. (2006). Lymphangioleiomyomatosis. Cancer control, 13(4), 276-285.Cooley, J., Lee, Y. G., & Gupta, N. (2017). Spontaneous pneumothorax in diffuse cystic lung diseases. Current opinion in pulmonary medicine, 23(4), 323.(4) Cooley, J., Lee, Y. G., & Gupta, N. (2017). Spontaneous pneumothorax in diffuse cystic lung diseases. Current opinion in pulmonary medicine, 23(4), 323.(5) Zhou, L., Ouyang, R., Luo, H., Ren, S., Chen, P., Peng, Y., ... & Liu, G. (2018). Efficacy of sirolimus for the prevention of recurrent pneumothorax in patients with lymphangioleiomyomatosis: a case series. Orphanet journal of rare diseases, 13(1), 168.(6) Taveira-DaSilva, A. M., Stylianou, M. P., Hedin, C. J., Kristof, A. S., Avila, N. A., Rabel, A., ... & Moss, J. (2003). Maximal oxygen uptake and severity of disease in lymphangioleiomyomatosis. American journal of respiratory and critical care medicine, 168(12), 1427-1431.(7) Riojas, R. A., Bahr, B. A., Thomas, D. B., Perciballi, J., & Noyes, L. (2012). A case report of lymphangioleiomyomatosis presenting as spontaneous pneumothorax. Military medicine, 177(4), 477-480.(8) Tanaka, H., Imada, A., Morikawa, T., Shibusa, T., Satoh, M., Sekine, K., & Abe, S. (1995). Diagnosis of pulmonary lymphangioleiomyomatosis by HMB45 in surgically treated spontaneous pneumothorax. European Respiratory Journal, 8(11), 1879-1882.(9) Martignoni, G., Pea, M., Reghellin, D., Gobbo, S., Zamboni, G., Chilosi, M., & Bonetti, F. (2010). Molecular pathology of lymphangioleiomyomatosis and other perivascular epithelioid cell tumors. Archives of pathology & laboratory medicine, 134(1), 33-40.(10) Chiappetta, M., Ferretti, G. M., Pogliani, L., Zanfrini, E., Iaffaldano, A., Nachira, D., & Margaritora, S. (2019). A 46-Year-Old Woman With an Uncommon Case of Massive Pneumothorax. Chest, 155(2), e25-e28.

C)

Figure 2: Histological staining of a patient

with LAM.

C) Lung biopsy with proliferation of spindle-

shaped myoid cells placed in fascicles

surrounding venous structures (10).

Lymphangiomyomatosis Management

References