Lymphangitis carcinomatosa

Lymphangitis carcinomatosa also known as carcinomatous lymphangitis, is an inflammation of the lymph vessels secondary to a malignancy. Lymphangitis carcinomatosa was first discovered by Gabriel Andral, a French pathologist, in 1829. The pathogenesis of lymphangitis carcinomatosa is characterized by the tumoral spread into the lymphatics, following hematogenous seeding of the lungs. The pathogenesis is also characterized by retrograde spread into lymphatics from the mediastinal and hilar lymph nodes in the lungs. Common causes of lymphangitis carcinomatosa include breast cancer (most common), lung cancer, colon cancer, stomach cancer, prostate cancer, cervical cancer, and thyroid cancer. Lymphangitis carcinomatosa is a rare disease. The prevalence of lymphangitis carcinomatosa is approximately 0.03 per 100,000 individuals worldwide. Lymphangitis carcinomatosa is more commonly observed among patients aged between 40 to 49 years old. Computed tomography is the imaging modality of choice for lymphangitis carcinomatosa. On CT, characteristic findings of lymphangitis carcinomatosa include subpleural nodules, thickening on the interlobar fissures, pleural effusion, and hilar and mediastinal nodal enlargement (40-50%). The mainstay therapy for lymphangitis carcinomatosa is systemic chemotherapy (chemotherapeutic regimen depends on the tumor histology).

• Lymphangitis carcinomatosa was first discovered by Gabriel Andral, a distinguished French pathologist and professor at the University of Paris in 1829.^[1]
• Andral’s case report on postmortem findings of lymphangitis carcinomatosa followed after a case report on a woman who had died from cancer of the uterus; there had been extensive spread of the cancer in the pelvis, mesentery and thoracic duct-there was no mention of pulmonary or pleural involvement.^[2]
• Andral is remembered for his pioneer investigations of blood chemistry.
• Gabriel Andral is considered to be the founder of scientific hematology, and is credited with its integration into clinical and analytical medicine.

• There is no established system for the classification of lymphangitis carcinomatosa.^[3]

• It is understood that lymphangitis carcinomatosa is the result of the tumoral spread into the lymphatics, following hematogenous seeding of the lungs.^[4]
• The pathogenesis is also characterized by retrograde spread into lymphatics from the mediastinal and hilar lymph nodes in the lungs.^[5]
• Both the peripheral lymphatics coursing in the interlobular septa and beneath the pleura, and the central lymphatics coursing in the bronchovascular interstitium are involved.^[6]
• There are no specific genetic mutations associated with the development of lymphangitis carcinomatosa.^[7]
• On gross pathology, characteristic findings of lymphangitis carcinomatosa include:^[8]

• No remarkable findings

• On microscopic histopathological analysis, characteristic findings of lymphangitis carcinomatosa include:^[8]

• Carcinoma in multiple the lymphatic channels

• Common causes of lymphangitis carcinomatosa include:^[8]
  • Breast cancer (most common)
  • Lung cancer
  • Colon cancer
  • Stomach cancer
  • Prostate cancer
  • Cervical cancer
  • Thyroid cancer

• Lymphangitis carcinomatosa must be differentiated from other diseases that cause thickened interlobular septae (on imaging finding), dyspnea, fatigue, and weight-loss, such as:^[9][10]

• Sarcoidosis
• Pulmonary Alveolar Proteinosis
• Viral pneumonia; pneumocystis jirovecii
• Pulmonary edema
• Radiation pneumonitis
• Lymphocytic interstitial pneumonitis

• Pulmonary lymphangitic carcinomatosis occurs in 6%–8% of patients with pulmonary metastases.^[11]

• Lymphangitis carcinomatosa is a rare disease.^[12]
• The prevalence of lymphangitis carcinomatosa is approximately 0.03 per 100,000 individuals worldwide.^[13]

• Patients of all age groups may develop lymphangitis carcinomatosa.

• Lymphangitis carcinomatosa is more commonly observed among patients aged 40–49 years old.^[13]
• Lymphangitis carcinomatosa is more commonly observed among middle aged adults.

• The condition affects males more than the females
• Affects a younger population than that affected with most malignancies

• There is no racial predilection for lymphangitis carcinomatosa.

• Common risk factors in the development of lymphangitis carcinomatosa include:^[13]

• Personal history of cancer
• Preexistent malignant cancer

• The majority of patients with lymphangitis carcinomatosa are symptomatic at the time of diagnosis.^[14]
• There are two theories as to how this condition occurs^[15]
  • The first theory states there is haematogenous metastasis producing obliterative endarteritis and then tumor cells subsequently egress through vascular walls into the perivascular lymphatics.
  • The second theory states there may be diffuse retrograde permeation and embolization of lymphatics after involvement of the hilar lymph nodes.
• Early clinical features include dyspnea, fatigue, and weight-loss.
• Lymphangitis carcinomatosa may precede or obscure or dominate any local symptoms and present as a diagnostic problem in dyspnoea.^[16]
• Lymphangitis carcinomatosa may also occur during the evolution of a growth, which has already been identified during life, in which case diagnosis becomes relatively easier.
• If left untreated, patients with lymphangitis carcinomatosa may progress to develop acute respiratory failure.
• Common complications of lymphangitis carcinomatosa include:^[9]

• Pulmonary tumor embolism
• Pulmonary hypertension

• Prognosis is generally poor, and the mean survival rate of patients after diagnosis of lymphangitis carcinomatosa is approximately 6 months.
• Approximately half of patients succumbing to their illness within a year of diagnosis.
• Occasionally, long-term survival is encountered.

• The majority of patients with lymphangitis carcinomatosa are asymptomatic.
• Lymphangitis carcinomatosa is usually asymptomatic.^[17]
• Symptoms of lymphangitis carcinomatosa may include the following:^[13]

• Hemoptysis
• Chronic coughing
• Chest pain
• Loss of appetite
• Fatigue

• Patients with lymphangitis carcinomatosa usually appear pale and malnourished.
• Physical examination may be remarkable for:^[13]

Auscultation

• Present pleural friction rub
• Present egophony
• Crackling or bubbling noises
• Present whispered pectoriloquy
• Decreased/absent breath sounds

Percussion

• Dull percussion
• Reduced chest expansion

• There are no specific laboratory findings associated with lymphangitis carcinomatosa.^[18]
• Even if histologically confirmed, the chest radiograph is normal in 30–50% of cases.

• Computed tomography is the imaging modality of choice for lymphangitis carcinomatosa.^[13]
• The most important feature about CT scan is the detection of peripheral and central changes.
• On CT, characteristic findings of lymphangitis carcinomatosa include:^[13]

• Subpleural nodules, and thickening on the interlobar fissures
• Pleural effusion
• Hilar and mediastinal nodal enlargement (40-50%)
• Relatively little destruction of overall lung architecture
• Involvement of the peripheral (interlobular septa) and central lymphatic system
• Distribution of changes is variable, but most are asymmetric and patchy
• Usually bilateral (may be unilateral especially in cases of lung and breast cancer)

• Radiographic appearances can most easily be divided into those due to the involvement of the peripheral and central lymphatic system.^[19]
• Involvement may be diffusely of both, or predominantly of one compartment or the other.
• Distribution of changes is variable, but most are asymmetric and patchy; it is usually bilateral but may be unilateral, specifically in cases of lung and breast cancer.^[20]

• The mainstay therapy for lymphangitis carcinomatosa is systemic chemotherapy (chemotherapeutic regimen depends on the tumor histology).^[13]

• Surgery is not recommended for patients with lymphangitis carcinomatosa.

• There are no primary preventive measures available for lymphangitis carcinomatosa. ^[4]
• Once diagnosed and successfully treated, patients with lymphangitis carcinomatosa are followed-up periodically.
• Follow-up testing may include respiratory function tests and disease progression monitorization.