Lymphangitic Carcinomatosis: Lymphangitic Carcinomatosis: Some HRCT FindingsSome HRCT Findings

AkochiAkochi AgunwambaAgunwamba, Harvard Medical School Year III , Harvard Medical School Year III and Gillian Lieberman, MDand Gillian Lieberman, MD

Lymphangitic Carcinomatosis: Lymphangitic Carcinomatosis: OverviewOverview

Also known as “Also known as “lymphangiaticlymphangiatic spread of tumors”, “spread of tumors”, “lymphangitislymphangitiscarcinomatosacarcinomatosa”, or “”, or “lymphangiosislymphangiosis carcinomatosacarcinomatosa””

LC refers to the infiltration of pulmonary LC refers to the infiltration of pulmonary parenchymalparenchymal lymphatic lymphatic channels by tumor cellschannels by tumor cells

Usually spread to lungs is Usually spread to lungs is hematogenoushematogenous, while spread within , while spread within lungs is lymphangiticlungs is lymphangitic

Unilateral (primary lung cancer and breast carcinoma) Unilateral (primary lung cancer and breast carcinoma) involvement is less common than bilateral (Stomach, Pancreas, involvement is less common than bilateral (Stomach, Pancreas, Prostate, Cervical, Thyroid, Colon, or Adenocarcinoma from an Prostate, Cervical, Thyroid, Colon, or Adenocarcinoma from an unknown site)unknown site)

~80% of the ~80% of the mettastasesmettastases are are adenocarcinomasadenocarcinomas

Herold CJ, et al. “Lung metastases”. Eur. Radiol. 6, 596-606 (1996)

Menu of Radiological TestsMenu of Radiological Tests

Chest XChest X--ray (CXR)ray (CXR)–– ~50% of lymphangitic carcinomatosis patients appear normal on ~50% of lymphangitic carcinomatosis patients appear normal on

CXR CXR

High Resolution Computed Tomography (HRCT)High Resolution Computed Tomography (HRCT)–– Currently appears to offer the best combination of cost and Currently appears to offer the best combination of cost and

sensitivity. 8sensitivity. 8--74% better than CXR for lymphangitic carcinomatosis74% better than CXR for lymphangitic carcinomatosis

Positron emission tomography with radioPositron emission tomography with radio--labeled [18F]labeled [18F]--22--fluorofluoro--deoxydeoxy--DD--glucose (PETglucose (PET--FDG)FDG)–– Very expensive. Sensitivity appears to be identical to HRCT thouVery expensive. Sensitivity appears to be identical to HRCT though gh

experience with PETexperience with PET--FDG in diagnosing lymphangitic carcinomatosis FDG in diagnosing lymphangitic carcinomatosis is limitedis limited

Khan AN, et al. “Lymphangitic Carcinomatosis”. eMedicine - http://www.emedicine.com/Radio/topic416.htm. Accessed 7/19/2008

HRCT findings in Lymphangitic CarcinomatosisHRCT findings in Lymphangitic Carcinomatosis

Herold CJ, et al. “Lung metastases”. Eur. Radiol. 6, 596-606 (1996); Webb, RW et al. Thoracic Imaging: Pulmonary and Cardiovascular Radiology (2005)

Irregular, smooth or nodular thickening of interlobular septaIrregular, smooth or nodular thickening of interlobular septa

Irregular and nodular thickening of Irregular and nodular thickening of peribronchovascularperibronchovascular sheetssheets

Thickening of Thickening of centrilobularcentrilobular structures structures

Peripherally located wedge shaped densities representing edema Peripherally located wedge shaped densities representing edema from lymphatic destructionfrom lymphatic destruction

Pleural diseasePleural disease

Correct first diagnosis 40% of the timeCorrect first diagnosis 40% of the time

Lymphangitic Carcinomatosis : Clinical Lymphangitic Carcinomatosis : Clinical SymptomsSymptoms

The clinical symptoms often precede radiographic The clinical symptoms often precede radiographic abnormalities and include:abnormalities and include:–– BreathlessnessBreathlessness–– Dry coughDry cough–– Hemoptysis (unusual unless there is primary lung cancer)Hemoptysis (unusual unless there is primary lung cancer)

Screening for lymphangitic carcinomatosis occurs Screening for lymphangitic carcinomatosis occurs in the context of prior malignancyin the context of prior malignancy

British Thoracic Society and Standards of Care Committee, Thorax 1999;54;S1-S28

Copyright ©Radiological Society of North America, 2006

Webb, W. R. Radiology 2006;239:322-338

Anatomy of the Secondary Lobule and Acinus

Copyright ©Radiological Society of North America, 2006

Webb, W. R. Radiology 2006;239:322-338

Radiograph: 1-mm lung slice taken from peripheral lower lobe – showing secondary lobule

S Lobules are marginated by thin interlobular septa

V Pulmonary vein branches

B Bronchioles

A Centrilobular Pulmonary arteries

Copyright ©Radiological Society of North America, 2006 Webb, W. R. Radiology 2006;239:322-338

Pathology: Interlobular septal and peribronchovascular thickening in lymphangitic carcinomatosis

On cut lung surface, small white arrows point to thickened interlobular septa and large arrow points to thickened peribronchovascular interstitium

H&E specimen (10x). Black arrows point to nodules of tumor in interlobular septa & centrilobular peribronchovascular region.

Our Patient: 35 Our Patient: 35 y/oy/o woman with 2 lung woman with 2 lung nodules. Rest of history withheld for nownodules. Rest of history withheld for now

Below level of lesion

At level of lesion

Above level of lesion

NOTE: Inspecting level above and below suspected level of lesion helps distinguish between nodule and vessel.

Images from PACS BIDMC Courtesy Dr. Ferris

nodule

Axial C+ CT of the chest

Differential for solitary nodule Differential for solitary nodule

Malignancy (adenocarcinoma Malignancy (adenocarcinoma -- 40%, 40%, squamoussquamous cell carcinoma cell carcinoma -- 20%, large cell 20%, large cell carcinoma carcinoma -- 15%, 15%, bronchoalveolarbronchoalveolar carcinoma carcinoma -- 10%, solitary metastases)10%, solitary metastases)

Benign Benign neoplasmsneoplasms ((hamartomashamartomas, , lipomaslipomas, and , and fibromasfibromas))

Vascular lesions Vascular lesions -- ArteriovenousArteriovenous malformationmalformation

Infectious Infectious granulomasgranulomas -- Tuberculosis, atypical Tuberculosis, atypical mycobacterialmycobacterial infection, infection, histoplasmosishistoplasmosis, , coccidioidomycosiscoccidioidomycosis, and , and blastomycosisblastomycosis

Other infections Other infections -- AspergillomaAspergilloma, , ascarisascaris, , dirofilariasisdirofilariasis, , echinococcalechinococcal cyst, and cyst, and bacterial abscess bacterial abscess

Noninfectious Noninfectious granulomasgranulomas -- Rheumatoid arthritis, Wegener granulomatosis, and Rheumatoid arthritis, Wegener granulomatosis, and sarcoidosissarcoidosis

Developmental lesions Developmental lesions -- BronchogenicBronchogenic cyst cyst

Other conditions Other conditions -- Hematoma, Hematoma, bronchiolitisbronchiolitis obliteransobliterans--organizing pneumonia, organizing pneumonia, pseudotumorpseudotumor, pulmonary infarction, , pulmonary infarction, amyloidomaamyloidoma, rounded , rounded atelectasisatelectasis, and , and mucoidmucoidimpaction impaction

1. Manocha S, “Solitary Pulmonary Nodule.” eMedicine – accessed 7/21/2008

Our Patient: At 8 Our Patient: At 8 mthmth follow up, presents follow up, presents with tachycardia and with tachycardia and dyspneadyspnea

Images from PACS BIDMC Courtesy Dr. Ferris

Enlarged hilum

Filling defects

Peripheral opacities (probably cellular or fluid infiltrates)

Reformatted HR CTA Axial View of the chest

Our Patient: Also had diffuse pulmonary Our Patient: Also had diffuse pulmonary diseasedisease

Images PACS BIDMC Courtesy Dr. Ferris

Enlarged Hilum

Thickened Septa

Thickened centrilobar structures

Peripheral opacities (probably fluid or cellular infiltrates)

Axial C+ CT of the chest

Our Patient: Diffuse interstitial disease on Our Patient: Diffuse interstitial disease on reconstructed reconstructed SagittalSagittal C+ HRCT of the ChestC+ HRCT of the Chest

PACS BIDMC Courtesy Dr. Ferris

Diffuse nodular and septal infiltrates

Major fissure

Serial Slices from Reconstructed Sagittal C+ HRCT of the chest

Our Patient: Interstitial infiltrates on CXR Our Patient: Interstitial infiltrates on CXR and HRCT and HRCT

Images from PACS BIDMC Courtesy Dr. Ferris

Scapula

SVC Porta catheter

Mediastinal enlargement

Increased interstitial markings

Axial C- HRCT

Left Lateral CXRAP Frontal CXR

Differential for septal and centrilobar Differential for septal and centrilobar thickeningthickening

Smooth interlobar septal thickening: Smooth interlobar septal thickening: –– pulmonary edema, hemorrhage, or pulmonary edema, hemorrhage, or venoveno--occlusive disease; occlusive disease;

Lymphangitic carcinomatosis; Lymphangitic carcinomatosis; lymphangiomatosislymphangiomatosis; ; amyloidosisamyloidosis, pneumonia, alveolar , pneumonia, alveolar proteinosisproteinosis

Nodular interlobar septal thickening: Nodular interlobar septal thickening: –– Lymphangitic carcinomatosis; Lymphangitic carcinomatosis; lymphoproliferativelymphoproliferative disease disease

(e.g. lymphocytic interstitial pneumonia); (e.g. lymphocytic interstitial pneumonia); sarcoidosissarcoidosis; silicosis ; silicosis and coal workers pneumoconiosis; and coal workers pneumoconiosis; amyloidosisamyloidosis

Centrilobular nodules due to Centrilobular nodules due to perilymphaticperilymphatic disease: disease: –– Lymphangitic carcinomatosis; Lymphangitic carcinomatosis; sarcoidosissarcoidosis; silicosis, coal ; silicosis, coal

workers pneumoconiosis; lymphocytic interstitial pneumoniaworkers pneumoconiosis; lymphocytic interstitial pneumonia

Ikezoe J, et al. AJR 1995;165:49-52. Webb, W. R. Radiology 2006;239:322-338

Our Patient: Complete HistoryOur Patient: Complete History

The patient is The patient is s/ps/p right right colectomycolectomy for poorly for poorly differentiated signet cell differentiated signet cell mucinousmucinous carcinoma of the carcinoma of the terminal ileum; b/l terminal ileum; b/l salpingosalpingo--oopherectomiesoopherectomies for for metsmets. Mets to . Mets to hemidiaphragmhemidiaphragm, bladder, small , bladder, small bowel, and pelvic side wall also observed. She is bowel, and pelvic side wall also observed. She is currently undergoing chemo.currently undergoing chemo.

This combined with the CT findings makes the This combined with the CT findings makes the suspicion for metastasis to the lung and for suspicion for metastasis to the lung and for lymphangitic carcinomatosis very highlymphangitic carcinomatosis very high

Prognosis for Lymphangitic carcinomatosisPrognosis for Lymphangitic carcinomatosis

Usually very poor Usually very poor –– survival in monthssurvival in monthsIn a small 8yr study of 10 pts treated with In a small 8yr study of 10 pts treated with surgical resection of primary, chemo, and/or surgical resection of primary, chemo, and/or radiation radiation txtx, initially:, initially:–– Pulmonary Pulmonary SxsSxs regressed in 6regressed in 6–– Progressed in 2Progressed in 2–– Unchanged in 2Unchanged in 2–– Median survival post diagnosis was 13 Median survival post diagnosis was 13 mthsmths (range: 11(range: 11--

30mths)30mths)

Ikezoe J, et al. “Pulmonary Lymphangitic Carcinomatosis: Chronicity of Radiographic Findings in Long-Term Survivors”. AJR 1995; 165:49-52.

ConclusionsConclusions

Lymphangitic carcinomatosis spreads Lymphangitic carcinomatosis spreads hematogenouslyhematogenously to the lungs to the lungs and then invades the lymphatic vesselsand then invades the lymphatic vessels

The accumulation of tumor cells causes thickening of the The accumulation of tumor cells causes thickening of the secondary lobule interstitiumsecondary lobule interstitium

HRCT is currently the modality of choice for screening lymphangiHRCT is currently the modality of choice for screening lymphangitic tic carcinomatosis patientscarcinomatosis patients

The diagnosis of lymphangitic carcinomatosis requires a clinicalThe diagnosis of lymphangitic carcinomatosis requires a clinicalcontext that includes malignancy.context that includes malignancy.

The prognosis for lymphangitic carcinomatosis is poorThe prognosis for lymphangitic carcinomatosis is poor

ReferencesReferences

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Findings in LongFindings in Long--Term Survivors”. AJR 1995; 165:49Term Survivors”. AJR 1995; 165:49--52.52.11.11. Webb, WR “Webb, WR “ThinThin--Section CT of the Secondary Pulmonary Lobule: Anatomy and the Section CT of the Secondary Pulmonary Lobule: Anatomy and the

ImageImage——The 2004 The 2004 FleischnerFleischner Lecture”. Lecture”. Radiology 2006;239:322Radiology 2006;239:322--33833812.12. ManochaManocha S, “Solitary Pulmonary Nodule.” S, “Solitary Pulmonary Nodule.” eMedicineeMedicine --

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AcknowledgementsAcknowledgements

Dr. Clare Dr. Clare HorkenHorkenDr. Dr. GethinGethin WilliamsWilliamsDr. Diana Dr. Diana LitmanovichLitmanovichDr. Diana FerrisDr. Diana FerrisDr. Gillian LiebermanDr. Gillian LiebermanMs. Maria Ms. Maria LevantakisLevantakis