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FDG PET/CT in Primary Extranodal Non-Hodgkin’s Lymphoma: Imaging Spectrum and Diagnostic Challenges in the Head and Thorax
, Vineet Mishra4, Krishna Kant Bharadwaj1, Prasanta Kumar Pradhan2
*Corresponding author: Dr. Manish Ora, Department of Nuclear Medicine, Sanjay Gandhi Postgraduate Institute of Medical Sciences (SGPIMS), Lucknow, Uttar Pradesh, India. drmanishora@gmail.com
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Received: ,
Accepted: ,
How to cite this article: Singh P, Sharma S, Pavecha P, Ora M, Datta G, Mishra V, et al. FDG PET/CT in Primary Extranodal Non-Hodgkin’s Lymphoma: Imaging Spectrum and Diagnostic Challenges in the Head and Thorax. Indian J Nucl Med. 2026;41:423-32. doi: 10.25259/IJNM_15_2026
Abstract
Primary extranodal non-Hodgkin’s lymphoma (eNHL) represents a heterogeneous group of lymphoid malignancies originating in tissues other than lymph nodes. 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) is integral to the staging and assessment of response in nodal lymphomas. However, its application in eNHL is intricate due to distinctive challenges arising from diverse anatomical locations, variable histology, and the mimicking of physiologic, inflammatory, and other malignant pathologies. This review aims to provide a comprehensive overview of the FDG PET/CT imaging spectrum of eNHL across various organs. We will highlight the presentation and site-specific diagnostic challenges and pitfalls. It will provide imaging insights to enhance accuracy in patient management. We retrospectively evaluated the case records of all histopathologically proven eNHL that underwent FDG PET/CT at two tertiary care institutions. Selected cases have a wide range of common and rare extranodal sites, head and neck, gastrointestinal tract, central nervous system, bone, and other rare locations. The Literature Search was done on PubMed, Embase, and Scopus databases. For each site, we discuss brief epidemiology, case presentation, and differential diagnosis. FDG PET/CT is a crucial functional imaging modality for evaluating eNHL, providing critical information for staging and individualised management. However, a profound insight into site-specific imaging patterns and diagnostic pitfalls is paramount for accurate interpretation and to avoid misdiagnosis.
Keywords
Diagnostic pitfalls
FDG
Non-Hodgkin's lymphoma
Oncologic imaging
PET/CT
Primary extranodal lymphoma
INTRODUCTION
Non-Hodgkin's lymphoma (NHL) comprises a diverse group of malignancies of lymphoid tissue with a global incidence of 18.7 per 100,000 per year.[1,2] Most NHLs arise in lymph nodes or other lymphatic tissues, such as the spleen, Waldeyer's ring, and thymus. Involvement of extranodal organs is common. Primary extranodal NHL (eNHL) is defined by exclusive extranodal origin without disseminated nodal disease and accounts for 10–35% of all NHL.[3,4] The gastrointestinal tract is the most frequent site, particularly the stomach, followed by the small and large intestine, representing 30–40% of primary eNHL. Other common sites include the head and neck (20–30%), followed by skin, central nervous system, breast, bone, thyroid, lung, and testis.[3,5] Histologically, diffuse large B-cell lymphoma (DLBCL) constitutes the majority (50–70%), followed by marginal zone lymphoma, follicular lymphoma, and extranodal NK/T-cell lymphoma.[6] Survival is primarily determined by Ann Arbour stage and histologic subtype rather than site. The five-year overall survival rate for localised eNHL ranges from 60% to 80%, depending on the subtype, International Prognostic Index (IPI) score, staging, and the organ involved. High mortality is noted with disseminated disease, high IPI scores, and in specific sites (e.g., central nervous system (CNS), bone marrow).[7,8]
Diagnosing eNHL is particularly challenging due to its heterogeneous clinical presentation, variable sites of origin, and diverse histopathology. Contrast-enhanced computed tomography (CT) is the first-line imaging modality, particularly for localisation, staging, and biopsy guidance. Magnetic resonance imaging (MRI) is particularly valuable for head and neck, CNS, and musculoskeletal eNHL due to its excellent soft-tissue resolution. For staging, sensitivity and specificity are 90% (95%CI 0.74–0.96) and 100% (95%CI 0.99–1.00).[9,10] However, CT and MRI have limitations of regional assessment, difficulties in the detection of multifocal, bone marrow, or non-enlarged parenchymal organ lesions. FDG PET/CT has become the standard for staging, extranodal involvement assessment, and interim and end-of-treatment response evaluation in aggressive NHL. It offers superior sensitivity for detecting metabolic activity in extranodal sites compared to anatomical imaging alone.[11,12] In contrast to the undebatable utility of FDG PET/CT in nodal NHL, its application in eNHL is less standardised and presents unique interpretive challenges. The heterogeneity of extranodal sites, variable avidity across histologic subtypes, and benign or inflammatory mimics pose challenges. The current literature is limited primarily to site-specific reports or small retrospective series, lacking a systematic, imaging-oriented overview.
This study aims to create a comprehensive, image-based review of the FDG PET/CT findings in eNHL. This study aims to identify site-specific imaging patterns, diagnostic challenges, differential considerations, and pitfalls that are essential for guiding clinical practice and enhancing diagnostic confidence in managing eNHL.
Material and methods
We retrospectively evaluated case records of all histopathologically proven eNHL that underwent FDG PET/CT in the Department of Nuclear Medicine. Cases were selected to demonstrate a wide range of common and rare extranodal sites and to highlight specific diagnostic challenges. We included NHL cases with exclusive involvement of extranodal sites or with regional lymph nodal involvement. We excluded NHL with lymph node-dominant disease with secondary involvement of extranodal sites. Keywords used: (“extranodal lymphoma”) And (“PET/CT” OR “FDG-PET” OR “positron emission tomography”). For discussion articles in English, published between 2000 and 2025, and primarily focusing on imaging, were utilised. The cases are being discussed in terms of site-specific imaging findings and challenges.
RESULTS AND DISCUSSION
Head and neck
Central nervous system
Primary central nervous system lymphomas (PCNSL) involve the brain, spinal cord, or leptomeninges and account for 4%–6% of all eNHL.[13] The most common histopathological variant is DLBCL. Lesions are mostly supratentorial, periventricular, and located in deep white matter, basal ganglia, or corpus callosum. Symptoms depend on location and include focal neurological deficits, neuropsychiatric changes, raised intracranial pressure (headache, vomiting), and seizures.[14] On CT or MRI, PCNSLs classically demonstrate intense and relatively homogeneous contrast enhancement, a feature attributed to the disruption of the blood-brain barrier. They are isointense to hypointense on T1, hyperintense on T2, and show restricted diffusion, reflecting the high cellularity and densely packed nature of the tumour. Imaging differentials include high-grade glioma (characterised by central necrosis and heterogeneous enhancement), metastases, demyelinating disease (tumefactive multiple sclerosis), abscess, and toxoplasmosis (characterised by ring enhancement in immunocompromised patients)[15] [Fig 1].
Pineal gland
Primary lymphoma of the pineal gland is a sporadic ENHL [Fig 1, lower row]. Imaging features are analogous to PCNSL. Differential diagnoses include germinoma (younger age, calcification, and elevated AFP/β-HCG levels), pineocytoma (a more circumscribed and benign tumour), pineoblastoma (in paediatric patients and with calcification), and metastasis[16,17] [Fig 2].
Orbit
Orbital eNHLs are rare, predominantly marginal zone B-cell lymphoma. It affects older adults (median age ~57), with unilateral orbital involvement. Symptoms include a painless orbital mass, proptosis, restricted eye movements, and eyelid swelling.[18,19] CT and MRI scans reveal a homogeneous, well-circumscribed mass that conforms to the shape of the globe and the adjacent bony orbit, displacing structures rather than invading or destroying them. MRI reveals an isointenseto-hyperintense signal on T2, moderate enhancement, and restricted diffusion. Differentials include pseudotumour (IgG4-related disease, characterised by pain, inflammation, and rapid onset), benign tumours, metastasis (manifesting as irregular margins, bony destruction, and multifocal involvement), and lymphoid hyperplasia[20] [Fig 3A and B].
Lacrimal gland
Primary eNHL of the lacrimal gland is rare, representing a small fraction of orbital lymphomas. They present as a painless, firm orbital mass, proptosis, and eyelid swelling. Marginal zone/mucosa-associated lymphoid tissue (MALT) and DLBCL are the most frequent histologies.[21] Imaging shows a homogenous, well-defined mass displacing adjacent structures without destruction.[22] Main radiological and clinical differentials include lymphoid hyperplasia, Sjögren's syndrome, sarcoidosis, and orbital pseudotumour[22,23] [Fig 3C and D].
Nasopharynx
Nasopharyngeal eNHL accounts for a minority of nasopharyngeal malignancies. The most common variant is DLBCL, followed by NK/T-cell and MALT lymphoma. Patients are adults (mean age ~60), with a male predominance. Symptoms include nasal obstruction, epistaxis, painless lymphadenopathy in the neck, and hearing loss.[24] Imaging features include a bulky, homogeneous, and symmetric mass with marked enhancement and minimal infiltration.[25] Radiological differentials include carcinoma (characterised by asymmetry, invasive features, and a classic origin from the fossa of Rosenmüller), juvenile nasopharyngeal angiofibroma (typically found in young males, characterised by intense vascularity), benign hyperplasia, and sarcomas[26] [Fig 4].
Sinonasal
Sinonasal eNHL represents only 1–5% of sinonasal malignancies, with DLBCL and NK/T-cell lymphoma being the most common subtypes. Symptoms are nonspecific and include nasal obstruction, epistaxis, rhinorrhea, facial swelling, headache, and, rarely, proptosis and cranial nerve palsy.[27,28] Imaging reveals a homogeneous, submucosal soft-tissue mass that causes expansion and local infiltration, often resulting in remodelling of the bone. DLBCL commonly involves the maxillary sinus, while NK/T-cell lymphoma tends to favour the nasal cavity [28,29] Radiological differentials include squamous cell carcinoma (ulcerative, associated with bone destruction), invasive fungal sinusitis (characterised by immunosuppression and black necrotic tissue), esthesioneuroblastoma (located in the olfactory groove, typically with a dumbbell shape), and polyps[29] [Fig 5].
Tonsils
Primary tonsillar eNHL constitutes approximately 50% of head and neck eNHL. Histopathology includes DLBCL, followed by marginal zone/MALT and mantle cell lymphoma. The median age is 52–58 years, with a slight male predominance. Patients usually present with unilateral tonsillar enlargement, throat pain, dysphagia, lymphadenopathy, or airway symptoms.[30] CT reveals a unilateral or bilateral, homogenous, slightly enhancing mass. MRI shows low-to-intermediate T1 and mildly hyperintense T2 signal, homogeneous enhancement, with restricted diffusion.[31,32] The main differentials include squamous cell carcinoma (irregular, ulcerative, and destructive), chronic tonsillitis (characterised by calcification, bilateral, and symmetric), and follicular hyperplasia (bilateral and symmetric).[30] [Fig 6A and B]
Thyroid
Thyroid eNHL is uncommon, constituting 2–5% of thyroid cancers and <2% of all eNHL. Patients are primarily older women (median age, 60–75 years) and arise in a background of Hashimoto's thyroiditis. These present as an enlarging painless mass, with compressive symptoms like dysphagia, hoarseness, or dyspnea. Most are DLBCL or MALT.[33] Ultrasound shows markedly hypoechoic, homogeneous masses with enhanced echoes. CT shows hypodense, well-circumscribed masses. MRI shows iso- to hypointense masses with homogeneous enhancement.[34] Differentials include well-differentiated thyroid carcinoma (unilateral mass and slow growing), anaplastic thyroid carcinoma (infiltrative, destructive, and rapidly progressive), Hashimoto's thyroiditis (chronic with deranged thyroid function), and goitre (nodular, non-infiltrative, with calcifications)[33,35] [Fig 6C and D].
Thorax
Pulmonary
Primary pulmonary lymphoma is a rare neoplasm, accounting for less than 1% of all lung malignancies and 3–4% of extranodal lymphomas. Most are B-cell lymphomas, with MALT lymphoma being the most frequent, followed by DLBCL.[36,37] They present with nonspecific symptoms such as cough, dyspnoea, chest pain, or haemoptysis.[36,37] The radiological appearance is diverse, with the most common pattern being a solitary nodule, followed by multiple nodules, mass-like consolidations, ground-glass opacities, or mixed patterns.[38] Differentials include primary lung carcinoma, infection (including tuberculosis and fungal), and organising pneumonia[38] [Fig 7].
Breast
Primary breast eNHL is a sporadic condition, representing <1% of all breast malignancies. The majority are DLBCL, marginal zone, or MALT. They typically affect middle-aged women and present with a unilateral, painless, rapidly enlarging breast mass.[39] Imaging features are often nonspecific. Mammography and ultrasound reveal a solitary, well-circumscribed, hypoechoic mass without microcalcifications or spiculation. On MRI, lesions appear hypointense on T1-weighted images and hyperintense on T2-weighted images, and exhibit variable enhancement.[40] Key differentials include breast carcinoma (spiculated margins, microcalcifications), phyllodes tumour, abscess (pain and fever), metastases, and primary sarcomas [Fig 8].
Chest wall
Primary chest wall eNHL involving the pleura, ribs, or soft tissues of the thoracic wall is extremely rare. Most cases are DLBCL and anaplastic large cell lymphoma, and may be associated with chronic pleural inflammation, prior tuberculosis, or pyothorax.[41] Patients present with chest pain, mass, or dyspnoea. Imaging shows a heterogeneous, soft-tissue mass along the chest wall. CT and MRI demonstrate invasion into ribs or soft tissues, rib destruction, and pleural effusion. A “pleural sandwich sign” refers to a mass enveloping the intercostal artery.[42] Key differentials include primary carcinomas (more destructive, with vascular invasion), sarcomas, metastasis, chronic empyema, and benign tumours (such as lipomas and neurogenic tumours)[42] [Fig 9A and B].
Pleura
Primary pleural eNHL is extremely rare, accounting for less than 1% of all lymphomas. It presents a diagnostic challenge due to its nonspecific symptoms and imaging features. The most common histopathologies are DLBCL, follicular, and T-cell lymphoma. Symptoms include dyspnoea, cough, chest pain, and recurrent pleural effusion.[43] Imaging reveals pleural-based nodular or diffuse pleural thickening, with variable effusion.[43] Imaging differentials include benign mesothelial tumours, mesothelioma, metastatic disease, mesenchymal malignancies, and infection[44] [Fig 9C and D].
Learning Points: FDG PET/CT demonstrates diverse yet characteristic imaging patterns of primary extranodal NHL across head, neck, and thoracic sites. Awareness of site-specific metabolic patterns and common mimics is essential to avoid diagnostic pitfalls and improve interpretative accuracy. FDG PET/CT provides added value in staging, biopsy guidance, treatment response assessment, and detection of occult multifocal extranodal disease.
CLINICAL SIGNIFICANCE
This pictorial essay highlights the crucial role of FDG PET/CT in recognising the varied spectrum of extranodal lymphoma and differentiating it from infective, inflammatory, and other malignant conditions. Improved familiarity with these imaging patterns can facilitate early diagnosis, accurate staging, and optimised multidisciplinary management.
Author contributions:
PS: Conceptualisation, data collection, image interpretation, literature review, manuscript drafting, and final manuscript editing; SS: Data acquisition, literature review, preparation of imaging findings, and manuscript drafting; PP: Clinical evaluation, haematological correlation, patient management details, and critical revision of the manuscript; MO: Study supervision, imaging interpretation, conceptualisation, data collection, image interpretation, literature review, manuscript drafting, and final manuscript editing; GD: Clinical haematology workup, diagnostic correlation, patient management contribution, and manuscript review; VM: PET/CT interpretation, academic inputs, literature review, and critical manuscript revision; KKB: Data collection, literature review, and manuscript formatting; PKP: Overall supervision, study conceptualisation, expert review of imaging findings, and final approval of the manuscript.
Ethical approval:
Institutional Review Board approval is not required.
Declaration of patient consent:
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given consent for their images and other clinical information to be reported in the journal. The patient understand that the patient’s names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Conflicts of interest:
There are no conflicts of interest.
Use of artificial intelligence (AI)-assisted technology for manuscript preparation:
The authors confirm that there was no use of artificial intelligence (AI)-assisted technology for assisting in the writing or editing of the manuscript, and no images were manipulated using AI.
Financial support and sponsorship: Nil.
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