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Hoi See Tsao, Harvard Medical School Year III
Gillian Lieberman, MD
Hoi See Tsao, 2014 Gillian Lieberman, MD
April 2014
Understand the pathophysiology and anatomy of lymphadenopathy
Learn the menu of imaging tests for lymphoma
Learn how to interpret the most common imaging studies for lymphoma with accurate terminology
Learn the differential diagnoses for different types of lymphadenopathy and bowel wall thickening
Hoi See Tsao, 2014 Gillian Lieberman, MD
Patient presentation
Radiologic imaging
Relevant pathophysiology
Relevant anatomy
Menu of tests
Differential diagnosis based on imaging findings
Patient outcome
Hoi See Tsao, 2014 Gillian Lieberman, MD
Patient presentation
Radiologic imaging
Relevant pathophysiology
Relevant anatomy
Menu of tests
Differential diagnosis based on imaging findings
Patient outcome
Hoi See Tsao, 2014 Gillian Lieberman, MD
Previously healthy 75yo F presenting with 8 pound weight loss and fatigue over the past 4 months.
PMH, meds, allergies, social history noncontributory
Family History: ◦ Sister - thyroid cancer
◦ Son - skin cancer
◦ Older half brother - prostate cancer
◦ Older half brother – mesothelioma
◦ Aunt - leukemia
◦ Uncle - gastric cancer
◦ Uncle - pancreatic cancer
Hoi See Tsao, 2014 Gillian Lieberman, MD
Pertinent physical exam findings ◦ Fullness at base of the sternocleidomastoid on the L side
◦ Mobile 2cm L axillary node
Labs ◦ Elevated Beta-2 microglobulin at 5.4mg/L (normal: 0.8-
2.2 mg/L)
◦ CBC w/diff, renal function, LFTs, calcium, albumin, UA grossly normal.
Hoi See Tsao, 2014 Gillian Lieberman, MD
Patient presentation
Radiologic imaging
Relevant pathophysiology
Relevant anatomy
Menu of tests
Differential diagnosis based on imaging findings
Patient outcome
Hoi See Tsao, 2014 Gillian Lieberman, MD
Given mobile 2cm left axillary node physical exam finding, bilateral diagnostic mammogram was performed showing a 3 cm hypervascular solid mass in the lower left axilla suspicious for malignancy.
CT Thorax and Abdomen (imaging will be reviewed in upcoming slides)
Hoi See Tsao, 2014 Gillian Lieberman, MD
Hoi See Tsao, 2014 Gillian Lieberman, MD
AXIAL CT Thorax C+
Soft tissue mass displacing trachea to the right and compressing left thyroid lobe.
Left subclavian vein. BIDMC PACS
Hoi See Tsao, 2014 Gillian Lieberman, MD
AXIAL CT Thorax C+
Left axillary lymph node containing an area of low attenuation in its lateral portion most consistent with a focus of necrosis. BIDMC PACS
Hoi See Tsao, 2014 Gillian Lieberman, MD
AXIAL CT Thorax C+
Left axillary lymph node containing an area of low attenuation in its lateral portion most consistent with a focus of necrosis. BIDMC PACS
Hoi See Tsao, 2014 Gillian Lieberman, MD
AXIAL CT Abdomen C+
Multiple low-attenuation areas in the liver parenchyma that are too small to characterize. The largest lesion of the liver is measured as shown. The spleen is at the upper limit of normal size. Together with other findings, this is suggestive of multifocal malignancy. BIDMC PACS
Hoi See Tsao, 2014 Gillian Lieberman, MD
AXIAL CT Abdomen C+ at the level of the aortic diaphragmatic hiatus
Bulky retroperitoneal soft tissue mass measuring 3.5x5.5x7.5 cm (coronal not shown). The mass displaces the abdominal aorta and IVC anteriorly. Inferior splenic pole low attenuation focus could be a small hemangioma or a metastasis. BIDMC PACS
Hoi See Tsao, 2014 Gillian Lieberman, MD
AXIAL CT Abdomen C+ Numerous non continuous segments of bowel with
abnormal mural thickening.as.
BIDMC PACS BIDMC PACS
Hoi See Tsao, 2014 Gillian Lieberman, MD
AXIAL CT Abdomen C+
Numerous enlarged mesenteric lymph nodes. Largest node shown above.
BIDMC PACS
Hoi See Tsao, 2014 Gillian Lieberman, MD
AXIAL CT Abdomen C+ Numerous enlarged mesenteric lymph nodes.
BIDMC PACS BIDMC PACS
Radiology Report: 1. “L lower cervical mass with tracheal displacement” 2. “Retroperitoneal soft tissue mass at the level of the
aortic [diaphragmatic] hiatus displacing the aorta and IVC anteriorly”
3. “Non contiguous segments of bowel wall thickening and luminal dilitation with associated mesenteric lympadenopathy”
4. “Multiple hepatic low-attenuation lesions which are too small to characterize”
“Overall constellation of findings is most in keeping with lymphoma with left axillary, retroperitoneal, small bowel and mesenteric nodal involvement. Lesions in the liver remain indeterminate.”
Hoi See Tsao, 2014 Gillian Lieberman, MD
BIDMC PACS Radiology Report
Hoi See Tsao, 2014 Gillian Lieberman, MD
Pathology Report: ◦ “The combined morphological and
immunophenotypical findings are consistent with a large B cell lymphoma with aggressive features.”
Hoi See Tsao, 2014 Gillian Lieberman, MD
BIDMC Pathology Report
Hoi See Tsao, 2014 Gillian Lieberman, MD
Hoi See Tsao, 2014 Gillian Lieberman, MD
AXIAL FDG-PET A 5.1 x 3.2 cm left
cervical nodal conglomerate is markedly FDG avid (SUVmax 30.4). There is no abnormal FDG uptake elsewhere in the head or neck.
BIDMC PACS
Hoi See Tsao, 2014 Gillian Lieberman, MD
AXIAL FDG-PET
2.8 x 1.6cm left axillary lymph node is FDG avid (SUVmax 34.1).
BIDMC PACS
Hoi See Tsao, 2014 Gillian Lieberman, MD
AXIAL FDG-PET
Slightly more inferior on the left lateral chest wall is a 0.6 x 0.4cm FDG avid node (SUVmax 6.9).
BIDMC PACS
Hoi See Tsao, 2014 Gillian Lieberman, MD
AXIAL FDG-PET
A 5.8x3.3cm retrocrural mass is markedly FDG avid (SUVmax 35.1).
Hypodensities in liver are not FDG avid.
BIDMC PACS
Hoi See Tsao, 2014 Gillian Lieberman, MD
AXIAL FDG-PET
There are multiple FDG-avid mesenteric masses that are difficult to separate from the FDG-avid thickened bowel wall.
BIDMC PACS BIDMC PACS
Patient presentation
Radiologic imaging
Relevant pathophysiology
Relevant anatomy
Menu of tests
Differential diagnosis based on imaging findings
Patient outcome
Hoi See Tsao, 2014 Gillian Lieberman, MD
Neoplasm derived from cells that normally develop into T lymphocytes (cytotoxic T lymphocytes, helper T lymphocytes, or regulatory T lymphocytes) or B lymphocytes (including plasma cells)
Freedman et al., 2014 C
Mature B-cell neoplasms ◦ Diffuse large B-cell lymphoma
Mature T-cell and NK-cell neoplasms
Hodgkin’s lymphoma
Histiocytic/dendritic cell neoplasms
Posttransplantation lymphoproliferative disorders
Hoi See Tsao, 2014 Gillian Lieberman, MD
Campo et al., 2011
Kwee et al., 2008
Patient presentation
Radiologic imaging
Relevant pathophysiology
Relevant anatomy
Menu of tests
Differential diagnosis based on imaging findings
Patient outcome
Hoi See Tsao, 2014 Gillian Lieberman, MD
Hoi See Tsao, 2014 Gillian Lieberman, MD
McClain et al., 2014
Hoi See Tsao, 2014 Gillian Lieberman, MD
Daeubler et al., 2014
Hoi See Tsao, 2014 Gillian Lieberman, MD
McClain et al., 2014 Daeubler et al., 2014
Hoi See Tsao, 2014 Gillian Lieberman, MD
McClain et al., 2014
Hoi See Tsao, 2014 Gillian Lieberman, MD
Hoi See Tsao, 2014 Gillian Lieberman, MD
Lymph Notes, 2014
Hoi See Tsao, 2014 Gillian Lieberman, MD
Hoi See Tsao, 2014 Gillian Lieberman, MD
Teddy, 2014
Clinical lymphadenopathy = palpable enlargement (>1cm) of one or more lymph nodes.
Radiologically, lymphadenopathy size thresholds (always measured in short axis) vary depending on the region. ◦ Most cervical nodes: 10mm ◦ Submental, submandibular: 15mm ◦ Retropharyngeal: 8mm ◦ Mediastinal: 10mm ◦ Mesenteric: 3mm (up to 5mm in some hospitals)
Douketis, 2012 Gerstenmaier et al, 2014
Hoi See Tsao, 2014 Gillian Lieberman, MD
Compiled with information from Douketis, 2012
Patient presentation
Radiologic imaging
Relevant pathophysiology
Relevant anatomy
Menu of tests
Differential diagnosis based on imaging findings
Patient outcome
Hoi See Tsao, 2014 Gillian Lieberman, MD
CT and/or PET are imaging modalities of choice to establish baseline prior to treatment and for staging
PET ◦ Gallium scan used to be gold standard for cancer diagnosis
and staging, but is non-specific as it can indicate new or old infection, inflammation, or malignancy
◦ FDG is currently used as radiotracer as it is more specific and lymphoma is typically FDG-avid
◦ Current research into potential as a biomarker of response to chemotherapy
When available, combined PET-CT to measure disease activity.
Hoi See Tsao, 2014 Gillian Lieberman, MD
Kwee et al., 2008 Freedman et al., 2014 A Freedman et al., 2014 B
MRI (less often used) ◦ Limited due to lengthy imaging time, limited
availability, cost
◦ Superior soft-tissue contrast, but staging is based on size and location criteria which can be adequately assessed on CT
Hoi See Tsao, 2014 Gillian Lieberman, MD
Kwee et al., 2008 Freedman et al., 2014 A Freedman et al., 2014 B
Patient presentation
Radiologic imaging
Relevant pathophysiology
Relevant anatomy
Menu of tests
Differential diagnosis based on imaging findings
Patient outcome
Hoi See Tsao, 2014 Gillian Lieberman, MD
Hoi See Tsao, 2014 Gillian Lieberman, MD
Benign ◦ Infection
Bacteria, viral (EBV, HSV, CMV), mycobacterial (TB)
◦ Kimura disease
◦ AIDS-related lymphadenopathy
◦ Sinus histiocytosis (Rosai-Dorfmann disease)
Malignancy ◦ Metastases from head and neck tumors
◦ Lymphoma
◦ Kaposi sarcoma
Hoi See Tsao, 2014 Gillian Lieberman, MD
Weerakkody et al., 2014 A
Benign ◦ Mastitis
◦ Infection: TB, ipsilateral arm infection (cellulitis), silicone induced granulomatous adenitis
Malignant ◦ Metastasis from breast malignancy
◦ Melanoma
◦ Primary malignancy in ipsilateral arm
◦ Lymphoma: occasionally can be unilateral
Hoi See Tsao, 2014 Gillian Lieberman, MD
Weerakkody et al., 2014 B
Benign ◦ Mesenteric Adenitis: Classically seen with Yersinia infection ◦ AIDS: Secondary to TB, MAC, Kaposi sarcoma, HIV direct
infection ◦ Diverticulitis ◦ Ulcerative colitis ◦ Crohn’s disease ◦ Appendicitis
Malignant ◦ Lymphoma
Most common malignant cause of mesenteric lymphadenopathy (usually Non-Hodgkins Lymphoma). Often have node enlargement in other parts of body.
◦ Carcinoid tumors ◦ Small bowel tumors ◦ Colon cancer ◦ Pancreatic cancer
Hoi See Tsao, 2014 Gillian Lieberman, MD
Radiologypics, 2013
Hoi See Tsao, 2014 Gillian Lieberman, MD
Hoi See Tsao, 2014 Gillian Lieberman, MD
Fernandes et al, 2013
Hoi See Tsao, 2014 Gillian Lieberman, MD
Segmental or diffuse bowel wall thickening with symmetric homogeneous attenuation
Rarely obstructs the bowel lumen
Minimal fat stranding near thickened bowel segments
Large bulky retroperitoneal lymph nodes usually present adjacent to or in areas removed from a region of bowel wall thickening
Associated splenomegaly
Treated lymphoma = occasional calcifications in mesentery
Hoi See Tsao, 2014 Gillian Lieberman, MD
Macari et al, 2001
Other than using the WHO classification of neoplastic diseases of the lymphoid tissue, radiologists tend to divide lymphomas by location i.e. small bowel lymphoma, mediastinal lymphoma.
As our patient presented with lymphadenopathy of multiple anatomic sites, this is consistent with diffuse lymphoma. Our patient had no history of cancer to suggest metastasis.
Diffuse large B cell lymphoma confirmed with pathology of L axillary node biopsy.
Hoi See Tsao, 2014 Gillian Lieberman, MD
Patient presentation
Radiologic imaging
Relevant pathophysiology
Relevant anatomy
Menu of tests
Differential diagnosis based on imaging findings
Patient outcome
Hoi See Tsao, 2014 Gillian Lieberman, MD
She received appropriate treatment. CT scan 1 year after treatment showed no evidence of lymphoma and she remains in remission.
Hoi See Tsao, 2014 Gillian Lieberman, MD
Schedule of surveillance highly dependent on histology subtype of lymphoma and patient and provider comfort.
Relapse is much less likely to occur greater than five years after treatment.
Hoi See Tsao, 2014 Gillian Lieberman, MD
We learned the pathophysiology and anatomy of lymphadenopathy
We learned the menu of imaging studies for lymphoma We learned how to interpret the most common imaging
studies for lymphoma through examining imaging studies performed on our patient
We learned the differential diagnoses for different types of lymphadenopathy.
We learned to classify bowel wall thickening into focal or segmental/diffuse patterns to organize our thinking of differential diagnoses. In terms of segmental/diffuse patterns, we then further examined what additional imaging findings on CT suggest lymphoma rather than a benign cause of bowel wall thickening.
Hoi See Tsao, 2014 Gillian Lieberman, MD
Hoi See Tsao, 2014 Gillian Lieberman, MD
Hoi See Tsao, 2014 Gillian Lieberman, MD
Macari et al, 2001
Hoi See Tsao, 2014 Gillian Lieberman, MD
Macari et al, 2001
Hoi See Tsao, 2014 Gillian Lieberman, MD
Macari et al, 2001
Hoi See Tsao, 2014 Gillian Lieberman, MD
Macari et al, 2001
Campo, Elias, Swerdlow, Steven H., Harris, Nancy L., Pileri, Stefano, Stein, Harald, & Jaffe, Elaine S. (2011). The 2008 WHO classification of lymphoid neoplasms and beyond: evolving concepts and practical applications. Blood, 117(19), 5019-5032. doi: 10.1182/blood-2011-01-293050
Daeubler, B., & Gaillard, F. (2014). Lymph node levels of the neck. Retrieved April 19, 2014, from Radiopaedia.org website: http://radiopaedia.org/articles/lymph-node-levels-of-the-neck
Douketis, J. D. (2012, September). Lymphadenopathy. Retrieved April 19, 2014, from The Merck Manual for Health Care Professionals website: http://www.merckmanuals.com/professional/ cardiovascular_disorders/lymphatic_disorders/lymphadenopathy.html
A: Fernandes, Teresa, Oliveira, MariaI, Castro, Ricardo, Araújo, Bruno, Viamonte, Bárbara, & Cunha, Rui. (2014). Bowel wall thickening at CT: simplifying the diagnosis. Insights into Imaging, 1-14. doi: 10.1007/s13244-013-0308-y
B: Freedman, A. S., & Friedberg, J. W. (2014). Evaluation and staging of non-Hodgkin lymphoma. Retrieved April 19, 2014, from UpToDate website: http://www.uptodate.com/contents/ evaluation-and-staging-of-non-hodgkin-lymphoma?source=see_link&anchor=H13#H13
C: Freedman, A. S., & Friedberg, J. W. (2014). Initial treatment of advanced stage diffuse large B cell lymphoma. Retrieved April 19, 2014, from UpToDate website: http://www.uptodate.com/contents/ initial-treatment-of-advanced-stage-diffuse-large-b-cell-lymphoma?source=see_link&anchor=H2#H2
D: Freedman, A. S., Friedberg, J. W., & Aster, J. C. (2014). Classification of the hematopoietic neoplasms. Retrieved April 19, 2014, from UpToDate website: http://www.uptodate.com/contents/ classification-of-the-hematopoietic-neoplasms?source=search_result&search=lymphoma+definition&selecte dTitle=1~150#H8
Gerstenmaier, J. F., & Gaillard, F. (2014). Lymph node enlargement. Retrieved April 19, 2014, from Radiopaedia.org website: http://radiopaedia.org/articles/lymph-node-enlargement
Kwee, Thomas C., Kwee, Robert M., & Nievelstein, Rutger A. J. (2008). Imaging in staging of malignant lymphoma: a systematic review. Blood, 111(2), 504-516. doi: 10.1182/blood-2007-07-101899
Lymph Notes. (2012). The lymphatic system. Retrieved April 19, 2014, from Lymph Notes website: http://www.lymphnotes.com/article.php/id/151/
Macari, Michael, & Balthazar, Emil J. (2001). CT of Bowel Wall Thickening. American Journal of Roentgenology, 176(5), 1105-1116. doi: 10.2214/ajr.176.5.1761105
McClain, K. L., & Fletcher, R. H. (2014). Peripheral lymphadenopathy in children: etiology. Retrieved April 19, 2014, from UpToDate website: http://www.uptodate.com/contents/ peripheral-lymphadenopathy-in-children-etiology?source=search_result&search=lymphadenopathy+pathogene sis&selectedTitle=1~150
Radiologypics. (2013, March 14). Solution to unknown case #21 – mesenteric lymphadenopathy differential diagnosis. Retrieved April 19, 2014, from Radiologypics.com website: http://radiologypics.com/2013/03/14/mesenteric-lymphadenopathy-differential-diagnosis/
Teddy. (2014). Thoracic Duct. Retrieved April 19, 2014, from Anatomy Directory website: http://www.aokainc.com/thoracic-duct-image/
A: Weerakkody, Y. (2014). Differential diagnosis of adult cervical lymphadenopathy. Retrieved April 19, 2014, from Radiopaedia.org website: http://radiopaedia.org/articles/ differential-diagnosis-of-adult-cervical-lymphanopathy
B: Weerakkody, Y. (2014). Differential diagnosis of unilateral axillary lymphadenopathy. Retrieved April 19, 2014, from Radiopaedia.org website: http://radiopaedia.org/articles/ differential-diagnosis-of-unilateral-axillary-lymphadenopathy
Hoi See Tsao, 2014 Gillian Lieberman, MD
Dr. Katherine Troy
Dr. Gillian Lieberman
Dr. Priscilla J. Slanetz
Megan Garber
Hoi See Tsao, 2014 Gillian Lieberman, MD