Lung

Mesenchymal tumors

Lymphangioleiomyomatosis



Last staff update: 4 January 2024 (update in progress)

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PubMed Search: Lymphangioleiomyomatosis

Ali Alzeer, M.D.
Roseann I. Wu, M.D., M.P.H.
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Cite this page: Alzeer A, Wu RI. Lymphangioleiomyomatosis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lungtumorlymphangioleiomyomatosis.html. Accessed February 23rd, 2024.
Definition / general
  • Lung mesenchymal neoplasm that arises from abnormal smooth muscle cells around lymphatic vessels and causes parenchymal damage
Essential features
  • Rare cystic lung disease that causes progressive lung damage; mainly affects young females with tuberous sclerosis complex (TSC)
Terminology
  • LAM
ICD coding
  • ICD-O: 9174/3 - lymphangioleiomyomatosis
  • ICD-11: CB07.Z - lymphangioleiomyomatosis, unspecified
Epidemiology
Sites
Pathophysiology
Etiology
Clinical features
Diagnosis
  • Usually a clinical diagnosis
  • Multiple bilateral round lung cysts on high resolution computed tomography (CT) scan
  • Screening CT scans are recommended for females with tuberous sclerosis complex (Am J Respir Crit Care Med 2006;173:105)
Laboratory
Radiology description
Radiology images

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Computed tomography Computed tomography

Computed tomography

Prognostic factors
Case reports
Treatment
  • Relies on degree of lung function and extent of lung damage
  • Supportive therapy with bronchodilators or oxygen therapy (Thorax 2019;74:999)
  • Observation for patients with mild function impairment
  • mTOR inhibitors (sirolimus, everolimus): for symptomatic patients with severe lung damage and disease progression (N Engl J Med 2011;364:1595)
  • Lung transplantation for cases refractory to medical treatment
Gross description
Gross images

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Multiple cysts

Multiple cysts

Microscopic (histologic) description
  • Multiple thin walled cysts
  • Cysts are lined or surrounded by nodules of rounded or spindled smooth muscle-like cells with mixed eosinophilic or clear cytoplasm, without cytologic atypia or mitoses
  • Hemosiderin laden macrophages may be present as a clue to organized hemorrhage resulting from cysts infiltrating nearby vessels
  • Multinodular pneumocyte hyperplasia around cysts (found in TSC LAM more than sporadic lymphangioleiomyomatosis)
  • References: Semin Respir Crit Care Med 2020;41:256, Endocrinology 2016;157:3374
Microscopic (histologic) images

Contributed by Roseann I. Wu, M.D., M.P.H. and Yale Rosen, M.D.

Cystic lung with nodule

Multiple cysts

Multiple cysts

Cytology description
  • Well organized, globular cluster consisting of lymphangioleiomyomatosis cells enveloped by lymphatic endothelial cells (Acta Cytol 2009;53:402)
Cytology images

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Outer flattened cells

Outer flattened cells

SMA, HMB45, D20

SMA, HMB45, D2-40

Immunofluorescence description
Immunofluorescence images

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Lymphangioleiomyomatosis cells

LAM cells

Positive stains
Negative stains
Electron microscopy description
  • Lymphangioleiomyomatosis nodules are lined by type II pneumocytes with short microvilli and electron dense cytoplasmic lamellar bodies (Arch Pathol Lab Med 2000;124:1642)
Electron microscopy images

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Multiple cysts Multiple cysts

Type II pneumocytes in LAM nodule

Molecular / cytogenetics description
Videos

Virtual slide review of a case of lymphangioleiomyomatosis

Overview of radiographic features of lymphangioleiomyomatosis

Sample pathology report
  • Lung, right upper lobe, wedge biopsy:
    • Lymphangioleiomyomatosis (see comment)
    • Comment: Sections show cystic spaces replacing normal parenchyma. Some of the cystic spaces have mural nodules consisting of epithelioid and spindled cell proliferation. Lesional cells are immunoreactive with ER, SMA and MelanA. Control stains are satisfactory. The clinical presentation, morphology and immunohistochemical stains support the diagnosis above.
Differential diagnosis
Board review style question #1

A 44 year old woman who is a nonsmoker presented to the emergency department with acute chest pain after several months of progressive dyspnea. Physical examination was notable for diminished breath sounds on the right side. Computed tomography of the chest revealed a large pneumothorax and diffuse, intraparenchymal pulmonary cysts. The patient underwent mechanical pleurodesis and a wedge biopsy was performed. The biopsy specimens contained numerous thin walled cysts lined with spindle cells; on immunohistochemistry, the spindle cells coexpressed smooth muscle and melanocytic markers. What is the most likely diagnosis?

  1. Emphysema
  2. Lymphangioleiomyomatosis
  3. Metastasizing pulmonary leiomyoma
  4. Sarcoidosis
Board review style answer #1
B. Lymphangioleiomyomatosis. Answer A is incorrect because emphysema can present with pneumothorax and lung cysts on imaging but the process is usually more localized and most patients have a history of smoking. Additionally, cysts seen in emphysematous lung specimens represent lung parenchyma with cystic changes rather than lesional / neoplastic cells with the above mentioned immunophenotype. Answer D is incorrect because while sarcoidosis can present with shortness of breath and cystic changes in the lung, these changes are usually localized. Sarcoidosis patients usually have hilar adenopathy and fibrosis (not a finding in this patient). Answer C is incorrect because metastasizing leiomyoma is a diffuse process that can also be symptomatic and appear cystic; however, on immunohistochemistry, leiomyoma cells are not immunoreactive to melanocytic markers.

Comment Here

Reference: Lymphangioleiomyomatosis
Board review style question #2
A 44 year old woman who is a nonsmoker presented to the emergency department with acute chest pain after several months of progressive dyspnea. Physical examination was notable for diminished breath sounds on the right side. Computed tomography of the chest revealed a large pneumothorax and diffuse, intraparenchymal pulmonary cysts. The patient underwent mechanical pleurodesis and a wedge biopsy was performed. The biopsy specimens contained numerous thin walled cysts lined with spindle cells; on immunohistochemistry, the spindle cells coexpressed smooth muscle and melanocytic markers. What other findings may be seen on this patient's physical examination?

  1. Characteristic skin changes
  2. Fever
  3. Lower extremity swelling
  4. Tobacco stains
Board review style answer #2
A. Characteristic skin changes. Most likely this patient also has TSC gene mutations as these contribute to the development of lymphangioleiomyomatosis (LAM). Skin changes / lesions such as angiofibromas or hypomelanotic macules are hallmarks / diagnostic features of tuberous sclerosis complex. Answer B is incorrect because fever has not been described for this disorder. Answer C is incorrect because lower extremity swelling and smoking history may raise suspicion for pulmonary embolism. Answer D is incorrect because tobacco stains would raise suspicion for complicated emphysema.

Comment Here

Reference: Lymphangioleiomyomatosis
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