Imaging manifestations of extranodal lymphoma

CNS Lymphoma

• Intracerebral Involvement: Occurs in 10–15% of systemic lymphoma cases.
• Primary CNS Lymphoma: Rare, ~1% of non-Hodgkin lymphoma (NHL); mostly B-cell type.
• Secondary Lymphoma:
  • • two-thirds have leptomeningeal spread (cranial nerves, spinal cord, spinal roots).
    • one third present with parenchymal disease (single/multiple enhancing lesions ± leptomeningeal involvement).
  • Lesion Distribution: Mirrors underlying disease.
• Neuroimaging Features:
  • CT: High attenuation due to high cellularity; homogeneous contrast enhancement.
  • MRI: Well-defined, isointense–hypointense on T1, hypointense on T2; uniform contrast enhancement.
  • Common Locations: Supratentorial white matter (frontal/parietal lobes), subependymal regions, deep gray matter.
  • Useful sign: "Butterfly pattern" crossing the corpus callosum.^[1,11]

Fig 1: A 67-year-old man with DLBCL, initially involving the pituitary gland (history of surgical resection). Axial CT (non-contrast a, contrast-enhanced b): Shows multiple subcortical periventricular white matter lesions with a confluent appearance (arrows) and homogeneous, strong contrast enhancement (arrowheads). Axial T1-weighted contrast-enhanced MRI: Displays diffuse subependymal enhancement in the lateral (c) and fourth ventricles (f) (yellow arrowheads). A hyperattenuated lesion in the temporal lobe uncus is seen on non-contrast CT (d), with marked enhancement on contrast MRI (e) (blue arrows).

Fig 2: A 57-y.o man with CNS metastases from NHL. Axial T1-weighted image: Multiple hypointense nodular lesions in the right basal ganglia, internal capsule, and frontal white matter (arrowheads). T2-weighted image: Lesions appear slightly hyperintense (arrows). Contrast-enhanced T1-weighted image (C): Shows avid, homogeneous enhancement with significant vasogenic edema (asterisk). Diffusion-weighted imaging (DWI) (D): Displays restricted diffusion with high signal intensity, corresponding to low signal on the ADC map (E).

Head and Neck

• After the GI tract, the head and neck region is the most common extranodal site for NHL.
• Diffuse large B-cell lymphoma (DLBCL) is the most frequent histological type.
• The Waldeyer’s ring (including the tonsils) accounts for one-third of head and neck NHL cases.
• Other commonly affected sites: mandible, hard palate, nasopharynx [Fig.3], parotid gland, paranasal sinuses [Fig.4], thyroid gland [Fig.6], and orbit [Fig.5].
• MRI is useful for assessing local invasion or displacement of adjacent structures.^[10] 

Fig 3: 65 y.o. female with bilateral tonsillar hypertrophy, firm neck masses, and gastric ulcer (biopsy: diffuse large B-cell non-Hodgkin's lymphoma). Axial (A) and Coronal (B) CECT show nasopharyngeal and oropharyngeal asymmetry with enlarged pharyngeal and palatine tonsils (left > right) (arrows) and bulky laterocervical lymph nodes (arrowheads).

Fig 4: A 52-y.o male with a history of cutaneous T-cell lymphoma presented with an infiltrative mass in the anterior frontal region, invading the anterior wall of the frontal sinus, along with a spheno-ethmoidal lesion (white arrows). Both lesions show diffusion restriction on DWI (a) and ADC (b) sequences, with hyperintense signals on T2 FLAIR (c). After two months of chemotherapy, significant regression of the tumor lesions was observed (yellow arrows).

Intraorbital involvement in NHL: Rare condition.

• • Primary: Originates in the orbit, usually as MALT lymphoma.
  • Secondary: Spread from systemic NHL, often aggressive types like diffuse large B-cell lymphoma.
• Imaging Features:
  • CT: Well-defined, homogeneous mass [Fig.3a], with minimal or no bone destruction.^[1]

Fig 5: 55-y.o. female patient with marginal zone lymphoma, involving the intestines and muscles, now shows intraorbital involvement. (A) Axial and (B) sagittal CECT images show homogeneous lesions within the right eyelid and left intra-conal space (blue arrows), causing displacement of the medial rectus muscle

Thorax

• Extranodal Sites: Thymus, thyroid [Fig.6F], pulmonary parenchyma, pleura, pericardium, chest wall [Fig.6B,C], breast.
• Pulmonary involvement patterns:
  • Hilar nodal mass extension into lung parenchyma
  • Cavitating lung nodules
  • Persistent consolidation
  • Widespread pulmonary nodularity [Fig.6E]
  • Reticular patterns with interlobular septal thickening
• Chest Wall Involvement: Seen in aggressive disease, often with extensive intrathoracic involvement.
• Diagnostic Challenge: Due to overlapping pulmonary conditions in affected patients.^[2,9]

Fig 6: A 38-y.o man with Primary Mediastinal B-cell Lymphoma (PMBCL) involving the lungs and thyroid. NECT (A) and CECT (B, C) axial images: Show a low-density anterior mediastinal mass (blue arrows) extending into the chest wall (blue arrowheads). Axial CECT (soft-tissue window D, lung window E): Reveals multiple parenchymal nodules and macronodules in the lungs (white arrows). Axial CECT (F): Shows diffuse thyroid enlargement with homogeneous low attenuation, similar to surrounding muscles (yellow arrows).

Adrenal Gland

• Adrenal Involvement in NHL occurs in ~4% of cases.
• Bilateral Involvement: Occurs in ~50% of cases with adrenal involvement [Fig.7].
• Patterns of Involvement:
  • Well-defined, rounded homogeneous mass
  • Enlarged adrenal gland with preserved normal shape^[3]

Gastrointestinal Tract 

• Gastrointestinal (GI) Involvement in NHL: Occurs in 10–30% of cases.
• Common Sites (in decreasing frequency): Stomach, small bowel, pharynx, large bowel, esophagus.
• Secondary GI Involvement:
  • Common due to mesenteric/retroperitoneal lymph node origin and abundant GI lymphoid tissue.
  • Often affects multiple sites [Fig.8].
• Primary GI Lymphoma: Typically involves a single site [Fig.7].
• Imaging Features Suggestive of Lymphoma:
  • Bulky mass or diffuse infiltration
  • Preservation of fat planes, no obstruction
  • Multiple site involvement
  • Associated bulky lymphadenopathy ^[3,6,7]

Fig 7: A 32-y.o man with DLBCL of the stomach. Axial AP CT (a): Shows marked gastric wall thickening with a lobulated inner surface and a smooth, well-defined outer wall (white arrows), without obstruction. Homogeneous round lesions are seen in the adrenal glands (white arrowheads). Axial AP CT (b) after 3 months of chemotherapy: Shows remission of both the gastric mass and adrenal lesions (yellow arrows).

Fig 8: A 63-y.o man with known large B-cell lymphoma and secondary intestinal involvement. Axial (A) and Coronal (B) CECT images: Show nodular masses and significant mural thickening in multiple small intestine segments (blue arrows) without signs of obstruction. Also noted are bulky lymphadenopathies (blue arrowheads).

Liver and Spleen

• Spleen and Liver Involvement in NHL:
  • Spleen: Affected in 20–40% of cases
  • Liver: Involved in up to 15% of cases
• Patterns of Involvement:
  • Diffuse infiltration ± organomegaly 
  • Focal nodules [Fig.9]
• Focal Hepatosplenic Lymphoma:
  • Resembles metastases but typically smaller, homogeneous
  • Often associated with extensive, bulky coalescent lymph nodes
• Main differential diagnosis: Fungal Abscesses - Smaller, heterogeneous enhancement ^[2,3]

Fig 9: A 65-y.o woman presented with liver, spleen, tonsil, and gastrointestinal involvement. Biopsy of a latero-cervical lymph node confirmed diffuse large B-cell lymphoma (DLBCL). Initial CT (axial PVP, a): Reveals a large solitary liver mass without vascular invasion (white arrows) and multiple round, hypoenhancing lesions in the spleen (white arrowheads). Follow-up CT (axial PVP, after 4 months of chemotherapy): Shows near-complete resolution of the liver mass and complete resolution of splenic lesions (yellow arrow).

Peritoneum

• Rare presentation, often linked to high-grade primary gastrointestinal NHL.
• Radiologic Appearance: Can mimic peritoneal carcinomatosis.
• Patterns of Involvement:
  • Discrete nodules
  • Diffuse infiltrative mass
  • Ascites [Fig.10]^[3,4]

Fig 10: A 65-y.o woman with small cell NHL involving the spleen and peritoneum. Axial CECT of the abdomen (a, b) shows a solitary hypodense lesion in the inferior pole of the spleen (white arrow), bulky deposits in the mesentery and abdominal flanks (white arrowheads), and a large volume of ascites (asterisk).

Genitourinary System

• Renal Involvement in NHL: Occurs in 3–8% of cases; kidneys are the most commonly affected genitourinary organ.
• Patterns of Involvement:
  • Multiple circumscribed masses [Fig.11, 12]
  • Infiltration from adjacent lymph nodes
  • Solitary or perinephric masses
  • Diffuse infiltration [Fig.11]
• Differential Diagnosis:
  • Metastases: Similar appearance
  • Renal Cell Carcinoma: Hypervascular enhancement
  • Transitional Cell Carcinoma and Severe Pyelonephritis: Can mimic diffuse infiltration
• Diagnostic Clues for Lymphoma:
  • Bulky lymphadenopathy
  • Absence of infection signs
  • Patent renal hilar vessels despite encasement
  • Minimal hydronephrosis ^[3]

Fig 11: B-cell NHL in a 54-y.o female patient with bilateral kidney involvement. Coronal CECT (a): Shows multiple, bilateral, well-circumscribed hypoenhancing renal masses (white arrows). Follow-up Coronal CECT (b, after 3 months of antibiotics): Demonstrates disease progression with bilateral hypoenhancing renal masses showing a tendency to confluence. In a different patient with NHL: Axial (c) and Coronal (d) CECT (portal venous phase): Reveal poorly enhancing, infiltrative bilateral renal masses (orange arrows) with involvement of the extrarenal pelvis (orange arrowheads).

Pancreas

• Pancreatic Involvement in NHL: Occurs in ~30% of cases, usually from adjacent nodal infiltration.
• Patterns of Involvement:
  • Well-defined mass [Fig.12]
  • Diffuse gland enlargement, mimicking acute pancreatitis
• Key Features:
  • Bile duct obstruction may occur
  • Significant dilation of the main pancreatic duct is rare, even with large tumors ^[3]

Fig 12: 62 y.o. female patient with NHL with medium B cell. CECT (arterial phase, A): Shows a low-attenuation, poorly enhancing mass enlarging the pancreas (white arrow) and additional low-attenuation lesions in the upper poles of both kidneys (white arrowheads). MRI (Axial T1 in-phase, B & T2 HASTE, C): Reveals hypoenhancing focal lesions in the pancreatic body (white arrows) and renal parenchyma (white arrowheads). While differential diagnoses include diffuse infection, pyelonephritis, or metastases, the clinical presentation and widespread involvement are more consistent with lymphoma

Musculoskeletal System

Occurs as part of widespread disease.

Can result from:

• • • Direct extension from nearby lymphadenopathy [Fig.13d]
    • Spread from bone lesions

Primary muscle involvement (least common)

Commonly Affected Areas:

• • • • Thigh [Fig.13]
      • Upper limbs
      • Chest ^[2]

Fig 13: A 63-y.o man with right hip pain and swelling. NECT (a) and PVP CECT (axial b, coronal c): Show diffuse enlargement of the right obturator externus muscle with intense, homogeneous enhancement. Similar lesions (yellow arrowheads) are seen in the right rectus femoris (a, b, c), left piriformis (d), left gluteus maximus (e), and right paraspinal muscle (f). Marked splenomegaly is also noted (c, asterisk). A biopsy confirmed Peripheral T-Cell Non-Hodgkin Lymphoma.

Fig 14: 52-y.o male with classic mantle cell variant of small B-cell NHL. (A–D) Sagittal T1, T1 fat-saturated (pre/post-contrast), and T2 STIR sequences, along with axial T2 (E), reveal multiple confluent paravertebral thoracic masses predominantly along the lateral vertebral surfaces (arrows). These masses extend through the intervertebral foramina with intracanalicular involvement, causing thoracic spinal cord compression (arrowheads).

II. Differential diagnosis

Glioblastoma 

• Location: Cortical-subcortical junction, often crossing the midline (butterfly pattern).
• Margins: Irregular, infiltrative.
• Enhancement: Heterogeneous ring-enhancement with central necrosis.
• Necrosis/Edema: Common necrosis with extensive vasogenic edema.
• DWI: Variable; facilitated diffusion in necrotic areas.
• Leptomeningeal Involvement: Rare.    

Fig 15: Axial T2 FLAIR (A )and T1 post-contrast (B) images show a midline polylobulated mass extending into the right frontal lobe. It appears heterogeneous with irregular borders, T2 FLAIR hypersignal, intense peripheral gadolinium enhancement, central necrosis, surrounding vasogenic edema, and mass effect on the corpus callosum (arrows).

Gastric Adenocarcinoma 

• Often involves the antrum or pylorus.
• Irregular, asymmetric thickening with loss of normal gastric folds.
• Heterogeneous enhancement due to fibrosis, necrosis, or ulceration.
• Gastric Distensibility: Reduced due to fibrosis and infiltration
• Perigastric Fat Stranding: Suggests invasion beyond the gastric wall

Fig 16: Axial (A) and sagittal (B) venous-phase CT images show gastric wall thickening at the antrum-pyloric region, causing partial luminal stenosis with perigastric fat stranding and invasion into the pancreatic head (arrows).

Splenic Abcesses

• Hypodense lesions with fluid density, often multiloculated.
• Often irregular with heterogeneous density due to pus, debris, or necrosis.
• Possible central non-enhancing area representing pus or necrosis.
• Margins: Irregular or shaggy margins with surrounding inflammatory changes.
• History of infection, immunosuppression, trauma, or splenic infarction.

Fig 17: Axial (A) and coronal (B) CT images in the venous phase of a patient with known infectious endocarditis reveal a multiloculated, fluid-filled collection in the medial portion of the spleen (arrows).

Intrahepatic Cholangiocarcinoma 

Irregular, mass-forming lesion often with lobulated contours.

Heterogeneous density with areas of necrosis or fibrosis.

Enhancement Pattern:

• Peripheral rim enhancement in the arterial phase.
• Progressive, delayed central enhancement due to fibrous stroma.
• Capsular retraction overlying the tumor is common.

Bile duct dilatation proximal to the tumor due to obstruction.

Fig 18: Axial images in the arterial (A), venous (B), and delayed (C) phases show a polylobulated mass with irregular margins, peripheral arterial enhancement, and progressive contrast uptake (arrows), causing significant intrahepatic bile duct dilation (arrowheads).

Pancreatic Metastasis

• Typically hypodense nodules or masses, often multiple.
• Can appear as focal, well-defined lesions or diffuse infiltrative masses.

Enhancement Pattern (CT/MRI):

• Variable enhancement depending on the primary tumor origin (e.g., hypervascular from renal cell carcinoma, hypovascular from lung cancer).
• Often shows heterogeneous enhancement with possible central necrosis.

Margins: Well-defined in most cases, but can be irregular with infiltrative growth in aggressive metastases.

Associated Findings:

• Presence of metastatic lesions in other organs (liver, lungs, lymph nodes).
• History of a known primary malignancy.

Fig 19: Axial arterial phase CT images (a, b) of an 80-year-old male with a history of left nephrectomy for renal cell carcinoma (RCC) show focal, vividly enhancing lesions (arrows) within the pancreatic parenchyma, accompanied by central necrosis.