Head and Neck Imaging Conference University of Perineural Tumor Spread In Head & Neck Cancer Philip Chapman MD University of Alabama, Birmingham OBJECTIVES: 1. Define (PNTS) 2. Distinguish from pathologic term Perineural Tumor Invasion 3. Understand the disease impact of PNTS 4. Review the common pathways of PNTS 5. Discuss the CT and MRI findings of PNTS vs Invasion Histology of Perineural Tumor PNI is a histopathological tumor feature indicating direct involvement of microscopic nerves PNI is often used interchangeably with PNTS in the literature What is Perineural Invasion (PNI) described in the pathology report? SCCa SCCA Perineural Invasion Tumor along, within, or wrapping around a nerve Involvement of at least one-third of the circumference of the nerve by tumor cells is used as a surrogate if there is no obvious invasion of the nerve Histology of Perineural Tumor Perineural Invasion Some Tumor Cells are Neurotropic There is preferential growth along the nerve relative to other surrounding tissue types The epineurium and/or perineurium offers a growth advantage to tumor cells Active cross talk between the tumor and nerve cells through cytokines and proteins Perineural Invasion: What does it mean to the patient? Increased risk of local recurrence regional recurrence distant metastasis disease-specific mortality At, PNI is a trigger for additional/more aggressive treatment or at least more aggressive surveillance. 1
Radiologist s Definition of Is distinct growth pattern in which a malignant neoplasm spreads from a primary tumor site to a secondary site by way of a nerve Far less common than microscopic perineural invasion Refers macroscopic tumor growing along a nerve that is identified on CT or MRI large nerve named nerve Which cranial nerves? Virtually any of the cranial nerves can be affected Trigeminal Nerve Facial Nerve Cranial Nerve V is the nerve most commonly involved with PNTS V2, maxillary division, is the most commonly involved branch Symptoms are predominantly Sensory: Pain (misdiagnosed as Trig Neuralgia) Numbness Paresthesias Cranial nerve VII is second most commonly affected Symptoms are primarily motor: Facial weakness or paralysis Hemifacial spasm Malignancies with Perineural Tumor Spread in the Head and Neck Mucosal squamous cell carcinoma Skin malignancies Cutaneous squamous cell carcinoma and Melanoma Salivary gland malignancies Major salivary glands (esp Parotid) including adenoid cystic carcinoma Minor salivary (submucosal) Squamous cell carcinoma from either mucosa or skin will account for the majority of PNTS cases in a typical radiology practice Adenoid cystic carcinoma is particularly notorious for its neurotropic growth and PNTS 2
Other Malignancies Sarcoma (Rhabdomyosarcoma) Lymphoma Melanoma Mucoepidermoid Ca Acinic Cell Ca Salivary adenocarcinoma Basal Cell Carcinoma Clinical Radiological Correlation By the time patients have PNTS symptoms or signs, most will have MRI or CT evident PNTS Up to one-half of patients with radiographic evidence of PNTS may be asymptomatic Creeps in this pretty face from day to day Macbeth Creeps in this pretty face from day to day Macbeth Perineural Adenoid Cystic Carcinoma 45 yo presented with submucosal mass left hard palate Prior to imaging: Excisional Biopsy demonstrated Adenoid Cystic Ca Also had experienced intermittent paresthesias of left hard palate, upper lip, and cheek Minor Salivary Gland Tumors Minor salivary glands are most abundant in tongue base and hard palate The hard palate is the most common site of tumors Adenoid cystic carcinoma is most common malignancy PEARL: Many of these lesions remain submucosal so that diagnosis is delayed!! Creeps in this pretty face from day to day Macbeth Creeps in this pretty face from day to day Macbeth Minor Salivary Gland Tumors Minor salivary glands are most abundant in tongue base and hard palate The hard palate is the most common site of tumors Adenoid cystic carcinoma is most common malignancy Perineural Adenoid Cystic Ca PEARL: PNTS can be insidious (but relentless) over weeks, months or years before diagnosis is made T1 PRE 3
Perineural Adenoid Cystic Ca Creeps in this pretty face from day to day Macbeth Perineural Adenoid Cystic Ca Creeps in this pretty face from day to day Macbeth T1 POST NO FAT-SAT T1 PRE Creeps in this pretty face from day to day Macbeth Creeps in this pretty face from day to day Macbeth Perineural Adenoid Cystic Ca Perineural Adenoid Cystic Ca I have become comfortably numb Pink Floyd Tumor extends from one anatomic compartment or space to another Surgical cure more difficult Escapes local treatment effects Leads to disease persistence Disease progression 37 year old with Right Facial Anesthesia 4
I have become comfortably numb Pink Floyd I have become comfortably numb Pink Floyd Foramen Rotundum Vidian Canal Dx: Occult Adenoid Cystic Carcinoma of hard palate MRI MRI is generally more sensitive than CT in detecting all features of PNTS except for enlargement and erosion of bony foramina Often CT and MRI are complimentary Technical considerations for MRI include a small field of view (16-18 cm), thin slice (3 mm) and high-resolution matrix (min 256 x 256). Prefer 1.5T Start with axial and coronal T1 weighted images NO FAT SAT!! Post-contrast Fat-saturated T1 post contrast When I read an MRI of the neck or skull base, I spend 90% of my time reading the noncontrast T1 images P. Hudgins, Emory Univ Me too, then I use the other 90% looking at the post contrast images. P. Chapman : Artifacts Related to Fat Saturation Fat saturation after contrast? With fat sat, Left V2 is obscured by blooming artifact No fat sat clearly shows enlargement and enhancement with the foramen rotundum Pearl: Fat saturation is generally preferred for post contrast imaging for PNTS 5
Imaging Clues: The Nerve Itself Imaging Clues: The Nerve Itself Best Clue: Nerve is enlarged and demonstrates abnormal increased enhancement (CT or MRI) V3 V3 Adenoid Cystic Carcinoma that originated on hard palate, spread to Meckel s Cave, now down V3 Recurrent Parotid Adenocarcinoma with New Facial pain Other Imaging Clues: Abnormal erosion or widening of bony neural foramina, canals or fissures (CT) Site specific obliteration of fat planes Site specific soft tissue infiltration Muscular denervation Thickening and enhancement of the superficial muscular aponeurotic system (SMAS) Abnormal erosion or widening of neural foramina, canals, or fissures (CT) Cutaneous Melanoma with PNTS of vidian canal NPC with PNTS of Foramen Ovale Abnormal erosion or widening of neural foramina, canals, or fissures (CT) SCCA and widening of bony foramina/canals Foramen OH! vale Parotid Tumor V3 Pearl: Smooth Margins doesn t mean benign Adenoid Cystic Carcinoma of Parotid Gland 6
SCCA and widening of bony foramina/canals NF widening: Perineural Tumor Central Skull Base with response to therapy Alveolar Nerve Canal Erosion Cutaneous SCCA preauricular region with antegrade PNTS Site specific obliteration of fat planes (pads) Site (or space) specific soft tissue infiltration Imaging Clues: Site specific Target Sites for PNTS: PPF Pre antral fat pad Foramen ovale fat pad Mandibular foramen fat pad Stylomastoid foramen Masticator space Parotid Cavernous sinus Meckel s cave There are anatomic and nerve connections between the PPF and: Oral Cavity Nasal Cavity Nasopharynx Masticator Space Middle Cranial Fossa Orbit Pterygopalatine Fossa Muscular Denervation Secondary To Imaging Clues: Site specific Muscular denervation (chronic) PPF: 70 yr old male with NPC Obliteration of fat Enhancing soft tissue Widening of the fossa Neural Intersection Consider that tumor got to this location via PNTS or may travel from this location via PNTS PNTS involving V3 from adenoid cystic carcinoma of the oral cavity 7
Muscular Denervation Secondary To Muscular denervation (subacute) Increased Signal T2/STIR Abnormal Intramuscular Enhancement of Trigeminal Nerve V1 V2 V3 Subacute Denervation LEFT sec. to PNTS from NPC 62 year old male with history of SCCa of left forehead presented with left sided ptosis 8
Retrograde of V1 ***Most PNTS occurs in a retrograde direction toward the brainstem, but can be antegrade or birectional SCCA Two years later, following radiation to the orbit, patient presented with multiple left sided cranial neuropathies CN V (Trigeminal) SCCA V3 (Trigeminal) CN III (Oculomotor) CN V (Trigeminal) 9
PNTS from Cutaneous SCCA with multiple cranial nerves/branches and multiple directions V1 Cisternal CN V (Trigeminal) VI (Abducens) CN III (Oculomotor) V3 VI (Abducens) SCCA scalp with SCCA scalp with H/O Left Frontal SCCA Tumor Board Case 70 year old male with history of SCCA of the left forehead Returns to clinic with frozen globe on left SCCA scalp with SCCA scalp with Outside MRI read as normal. 10
SCCA scalp with V2 Absurdity can strike any man in the face A. Camus Infraorbital Nerve Absurdity can strike any man in the face A. Camus Infraorbital Nerve Elderly female with previous resection and radiation for upper right lip SCCA Presents with new fullness of right cheek and paresthesia in V2 distribution Preantral Fat Absurdity can strike any man in the face A. Camus Absurdity can strike any man in the face A. Camus Infraorbital Nerve Cutaneous SCCA with PNTS of Infraorbital Canal (Infraorbital Nerve) 11
I find doing speeches nerve wrecking. Kate Middleton 51 year old male with history of left facial SCCA Prior surgical resection, radiation, and parotidectomy ***New left facial pain Along V2 Teaching Point: Any new facial pain, numbness or paresthesia in patient with head and neck cancer should prompt a search for perineural tumor spread involving the trigeminal nerve 12
Outside Study: PNTS of Oral Cavity SCCA?? 35 year old female patient with history of childhood lymphoma of right sinus Radiation as child As teenager developed radiation induced sarcoma of masticator space Underwent resection and additional radiation Now with new imaging abnormality? Perineural Tumor Spread of Sarcoma up V3?? Concerns: Dural Vector Lack of new symptoms Radiation induced Meningioma Dx: Radiation Induced Meningioma Cranial Nerve VII (Facial nerve) is second most commonly affected nerve 13
Stylomastoid Foramen and Mastoid Segment The posteromedial parotid gland variably encroaches upon the stylomastoid foramen Fat within the stylomastoid foramen ( bell ) Obliteration of the fat can be key to identifying tumor extension to stylomastoid foramen and perineural tumor spread Adenocarcinoma Deep Parotid Adenocarcinoma Deep Parotid with PNTS of CN VII Adenocarcinoma Deep Parotid with PNTS of CN VII Classic Retrograde PNTS of CN VII 75 year old male with cutaneous SCCA of the external auditory canal, resection with radiation, then develops right facial nerve palsy 14
PNTS of Facial Nerve Heinz 57 Pattern of Teaching Point: The most common combination of cranial nerve spread involves CN V and CN VII Auriculotemporal Nerve Auriculotemporal Nerve V3 Auriculotemporal nerve Facial Nerve Caution: The auriculotemporal nerve: small not normally seen surrounded by extensive venous plexus that enhances Auriculotemporal nerve: Perineural SCCA Auriculotemporal nerve: Perineural SCCA 56 yo male with cutaneous SCCa of left ear Mets to parotid s/p parotidectomy, Postop radiation Then developed left facial pain and numbness V3 (Trigeminal) Auriculotemporal Nerve Facial Nerve 15
Auriculotemporal nerve: Perineural SCCA Auriculotemporal nerve: Perineural SCCA s/p Radiation: Abnormalities in 5 th nerve resolved Patient developed local recurrence and had salvage surgery with flap reconstruction and did well for app 1 year; developed pain in the mandible Tumor Recurrence along the inferior alveolar nerve of V3 Auriculotemporal nerve: Perineural SCCA God has given you one face Shakespeare Patient developed local recurrence and had salvage surgery with flap reconstruction and did well for app 1 year; developed pain in the mandible Basal Cell Ca, S/P Mohs 3 month FU, Progressive Facial Nerve Paralysis and ***Pain God has given you one face Shakespeare Auriculotemporal nerve: Perineural SCCA Auriculotemporal Nerve Squamous cell carcinoma of the left preauricular skin Treated with excision including left partial parotidectomy Now with left lower facial pain and paresthesia 16
Adenocarcinoma of Left Parotid Adenocarcinoma of Left Parotid Other lesions can mimic PNTS Schwannomas Meningiomas Pseudotumors Inflammation Infection Schwannoma Conclusion 1. Defined (PNTS) 2. Distinguished from Pathologic term Perineural Tumor Invasion 3. Reviewed the imaging anatomy of the cranial nerves susceptible to PNTS 4. Reviewed the common pathways of PNTS 5. Reviewed a number of actual cases, and discuss the CT and MRI findings of PNTS 17