1. Illustrate the characteristic imaging features of extranodal lymphoma of the head and neck (ENL-HN) with a variety of case examples based on anatomic pattern

2. Review the pathologic features of ENL-HN 3. Review differential diagnosis

EDUCATIONAL OBJECTIVES

INTRODUCTION

CONTACT

Lymphoma is the 2nd most common neoplasm of the head and neck, and up to 30% of the time it can present as an extranodal mass. Extranodal lymphoma of the head and neck (ENL-HN) may be seen in isolation or in conjunction with nodal disease. Disease sites include lymphoid tissue within Waldeyer’s ring or extralymphatic regions including the sinonasal cavity, salivary glands (SGs), orbit/ocular adnexa and the thyroid gland. ENL-HN may mimic other disease processes including other cancers, granulomatous disease and infection.

The clinical presentation of ENL-HN is variable with some tumors exhibiting an indolent course and others with more aggressive features. Risk factors include EBV, autoimmune disease, HIV and as a complication of immunosuppressive therapy. Staging is based on the Ann Arbor system.

Imaging evaluation of ENL-HN is performed with a combination of CT, MRI and FDG-PET . In general , ENL-HN presents as a bulky homogeneous submucosal mass. Ulceration is atypical. Aggressive forms may cause bony destruction. CT shows mild enhancement. MRI shows low T1, relatively low T2 , restricted diffusion (related to the tumor cellularity) with enhancement. Avid FDG uptake is typically seen on PET imaging.

PATHOLOGY

SUMMARY

Lymphoma should be considered in the differential diagnosis in a patient presenting with an extranodal soft tissue mass within the head and neck, especially in patients with predisposing risk factors. A comprehensive understanding of the varied imaging appearances of ENL-HN will enable the radiologist to accurately diagnose, stage and evaluate treatment response to this disease.

Tabassum A. Kennedy, MD University of Wisconsin-Madison Email: tkennedy@uwhealth.org www.radiology.wisc.edu

Extranodal Lymphoma of the Head and Neck Jill A. Hammersley MD, Tabassum A. Kennedy MD, Lindell R. Gentry MD, Michael J. Hartman MD

University of Wisconsin-Madison, Department of Radiology

Waldeyer’s ring: Nasopharynx (Fig 1, Fig 2) Palatine tonsils (Fig 1-4) Lingual tonsils (Fig 1) Clinical Features: - Most common site of ENL-HN - 2/3 of extranodal NHL in the H&N - 5% of all NHL - Painless, local swelling, sore throat - Hearing difficulties, nasal obstruction - 10% of patients have GI involvement. Differential: Squamous cell cancer (SCCa)

Imaging Features: CT/MR: More homogeneous and less intense enhancement than carcinomas. Bony destruction may be seen in high grade tumors .

WALDEYER’S RING

ORBIT/OCULAR ADNEXAE

Clinical Features: • Rapidly enlarging mass, dysphagia, hoarseness, choking, cold thyroid nodule. • Associated Hashimoto’s thyroiditis seen in 80% of patients • More common in women 70-80 years old Imaging:

US: Pseudocystic pattern with well defined, hypoechoic masses intermingled with echogenic areas (Fig 12). CT: Tumor often encircles trachea (Fig 12). More homogeneous than thyroid carcinoma. Calcifications and cystic degeneration are rare. MR: Similar signal intensity to underlying Hashimoto’s thyroidtitis.

SALIVARY GLAND

OTHER/SOFT TISSUE

THYROID

Fig 1: Mantle cell lymphoma of Waldeyer’s Ring. CT & MR images demonstrate massive enlargement of Waldeyer’s ring (A-E, arrows) including the adenoids (A, D, E), palatine (B) and lingual tonsils (C) . Note the extensive nodal involvement (B, C, arrows). Note the positive response to treatment on follow up imaging (F, arrow).

Fig 4: Tonsillar follicular lymphoma. Coronal post contrast CT (A) shows a mass centered within the left palatine tonsil (arrow). FDG-PET CT (B) demonstrates marked hypermetabolism within the mass (arrow).

Fig 3: Tonsilar PTLD in a renal transplant patient. FDG PET-CT shows marked FDG uptake in a right level IIa node (arrow) & within a mass centered within the right palatine tonsil (arrow).

SINONASAL

Fig 5: T cell Lymphoma of the paranasal sinuses. CT (A), T1 +C (B), T2 (C) and T1 W MR (D) images show an infiltrative enhancing mass within the left ethmoid sinus with involvement of the nasolacrimal duct (B, arrow). Notice how the mass extends through the lamina papyrecea into the superficial soft tissues (A, arrow). Note the relatively dark signal on T2 (C, arrow) as compared to adjacent T2 hyperintense inspissated secretiions.

Fig 12: Large B cell Lymphoma of the thyroid with bx proven Hashimotos thyroiditis. US (A) shows diffuse heterogeneous enlargement of the thyroid gland suggestive of hashimotos thyroiditis (arrows). CT (B, C) and PET (D) show diffuse enlargement of the thyroid gland (arrows) with a focal mass within the right upper pole (C, D, arrow). Also note the multiple enlarged lymph nodes within the right neck (C, D, arrows).

Imaging Features: - CT and MR show mildly enhancing submucosal soft tissue mass(es) often with nodal involvement. - Ulceration and bony destruction are atypical.

Clinical Features: Most common orbital malignancy in adults over 60. Enlarging, painless unilateral mass, proptosis without signs of inflammation. Vision loss rare. Four times more common in women. Location: Can involve the lacrimal gland (Fig 9) extraocular muscles (Fig 8), orbital fat (Fig 7,10), eyelids and conjunctiva (Fig 9). The most common location is the extraconal space of the superolateral orbit. Pathology: Almost always marginal zone (MALT type ) > Follicular B cell> Diffuse B cell

CT: Homogeneously high density with contrast enhancement. Bony erosion rare.

Imaging Features: MRI: T1- and T2- Intermediate intensity, homogeneous globular mass with moderate enhancement that encases orbital structures. Isointense to muscle.

Differential: Idiopathic orbital inflammation (pseudotumor), SCCa, infection

Imaging Features: CT/MR show solid, homogeneous mass with mild enhancement.

Differential: Metastatic disease, primary salivary gland neoplasm

Fig 15: Follicular lymphoma isolated to the parotid gland. PET-CT (A) and post contrast axial CT (B) of the neck shows a solid mass isolated to the left parotid gland (arrows). The mass has FDG uptake (A, arrow) on PET imaging. There are ill defined margins on contrast enhanced CT (B, arrow). The parotid gland was the only site of disease. Note the positive response to treatment on follow up imaging (C, arrow).

Fig 13: Lymphoma of the parotid gland and cervical nodes. Coronal (A) and axial (B, C) CT images of the neck show a large mass replacing the right parotid gland (arrows). The mass has ill defined margins. Note the extensive lymphadenopathy involving multiple nodal stations throughout the neck (arrows).

Fig 14: Isolated lymphoma of the parotid gland. Axial (A) CT image shows a large homogeneous mass replacing the left parotid gland (arrow). Other differential considerations include a salivary gland neoplasm and metastasis.

Fig 16: Lymphoma of the right frontotemporal scalp with intracranial extension in a 55 yo woman with HIV. Axial T1 +C (A), T2 (B) , DWI (C) MR, post contrast CT (D) and PET-CT CT (E) image show an infiltrative mass involving the right frontotemporal scalp (arrows). The lesion demonstrates heterogeneous enhancement (A, D, arrows) is relatively dark on T2 (B, arrow), shows extensive diffusion restriction (C, arrow) and avid FDG uptake (E, arrow). There is intracranial extension with dural enhancement (A, arrow). This lesion was initially suspected to be infection, but was biopsy proven NHL.

1. Aiken A, Glastonbury C. Imaging Hodgkin and Non-Hogkin Lymphoma in the Head and Neck. Radiol Clin N Am 2008;46:363-378.

2. Chua S, Rozalli F, O’Connor S. Imaging Features of Primary Extranodal Lymphoma. Clinical Radiology 2009;64:574-588.

3. Rademaker J. Hodgkin’s and Non-Hodgkin’s Lymphoma. Radiol

Clin N Am 2007;45:69-83.

4. Weber A, Rahemtullah A, Ferry J. Hodgkin andnon-Hodgkin lymphoma of the head and neck: clinical,pathologic, and imaging evaluation. NeuroimagingClin N Am 2003;13:371–92.

5. King A, et al. Non-Hodgkin’s lymphoma of the nasopharynx: CT and MR imaging. Clinical Radiology 2003;58:621–5.

6. Schoder H, et al. Effect of whole-body (18)F-FDG PET imaging on clinical staging and management of patients with malignant lymphoma. J Nucl Med 2001;42(8):1139–43.

7. Harnsberger H, et al. Non- Hodgkin’s lymphoma of the head and neck: CT evaluation of nodal and extranodal sites. AJR Am J

Roentgenol 1987;149(4):785–91.

REFERENCES

Fig 18: Lymphoma of premalar soft tissues. CT shows bilateral infiltrative masses within the premalar soft tissues (arrows). There is effacement of the adjacent fat planes.

Fig 17: B Cell lymphoma of the temporalis. CT (A) and PET images (B, C) show a soft tissue mass centered within the left temporalis muscle/scalp (arrows). Note the extensive extranodal disease within the pelvis and lower extremities (arrows).

Fig 2: PTLD of Waldeyer’s ring Axial post contrast CT (A, B) images show enlarged adenoids (A, arrows) and tonsils (B, arrows) in this 16 year old s/p lung transplant.

Fig 19: Lymphoma of the periorbital soft tissues. Contrast enhanced CT (A), T1 W (B), T1 +C (C) and DW MR (D) images demonstrate bilateral enhancing infiltrative bifrontal subcutaenous soft tissue masses adjacent to the orbital roof (arrows). These lesions restrict diffusion (D, arrows). Note the posterior extension through the supraorbital notch, right greater than left (C, arrows).

Fig 10: Orbital lymphoma. Axial and coronal MR and CT images show a relatively homogeneously enhancing mass within the intraconal retrobulbar space of the right orbit (A-D, arrows). There is resultant proptosis of the right globe. The mass is relatively dark on T2 (A, arrow). Note how the mass insinuates around the right optic nerve without frank involvement, (B, arrow).

Fig 11: Lymphoma of the lacrimal gland/ orbit. CT and MR images show an enhancing soft tissue mass centered within the left lacrimal gland (A-E, arrows). The mass extends into the intraconal space, is relatively dark on T2 (C, arrow) and restricts diffusion (E, arrow). Note the smaller retrobulbar lesion on the right (C, D, E, arrows)

Fig 9: Lymphoma of the globe & conjunctiva Axial CT shows asymmetric thickening of the right conjunctiva (arrow). Note the retinal detachment (arrow) and high attenuation within the anterior chamber (arrow). All of these findings can be seen with ocular lymphoma.

Fig 7: Lymphoma of the orbit. Axial (A) and sagittal (B) CT images show an infiltrative homogeneous enhancing soft tissue mass that involves both the inferolateral pre and post septal spaces (arrows) of the right orbit.

Fig 8: Lymphoma of the superior rectus. Coronal CT shows unilateral enlargement of the right superior rectus muscle (arrow).

Primary Lymphoma (Fig 14, 15) Secondary Lymphoma (Fig 13)

• Isolated to the salivary glands • Distribution: - 80% of the parotid glands - 20% submandibular glands • 20% of pts have autoimmune disease (Sjögren’s ) • Pathology: Most often MALT lymphoma • Prognosis: 60% 2 year survival

•Diffuse disease with salivary gland involvement •1-8% of all lymphomas •Pathology: not MALT lymphoma; usually a high grade diffuse large B cell lymphoma •Prognosis: typically poor due to presentation with high grade tumor.

Non-Hodgkin lymphoma (NHL) frequently presents with extranodal disease, occurring in up to 30% of patients. Hodgkin lymphoma (HL) however rarely presents with extranodal disease. The most common type of NHL seen in the head and neck is large B cell lymphoma which often involves Waldeyer’s ring, the paranasal sinuses and the mandible. Marginal zone (MALT type) lymphoma has a predilection for the orbit, salivary glands, thyroid and larynx whereas NK/T cell lymphoma is seen most often within the paranasal sinuses.

Fig 6: Sinonasal B cell lymphoma. T1 +C (A) & DWI (B) MRI show an infiltrative mass within the left nasal cavity & maxillary sinus extending into the masticator space (arrows). There is restricted diffusion & enhancement.

Differential: Anaplastic thyroid carcinoma, goiter.

A B C

D E F

A B

A B

A B C D

A B

A B

C D

E A B

C D

A B

A B A B C D

A B C

A C B D E A C B

A C B D

Other extranodal disease sites within the head and neck include the subcutaneous soft tissues (Fig 16-19), larynx, mandible and maxilla.

Clinical Features: Low grade tumors present with signs of obstruction. High grade tumors exhibit more aggressive features such as epistaxis & CN palsies.

Differential: SCCa, esthesioneuroblastoma, Wegener’s