Head And Neck Cancer, Non-Squamous

Todd M. Blodgett, MD

Alex Ryan, MD

Marios Papachristou, MD

Key Facts

Terminology

Neuroendocrine tumors (NET), small cell undifferentiated carcinoma, Merkel cell carcinoma (MCC)
Benign mixed tumors (BMT) or pleomorphic adenoma; Warthin tumor; parotid carcinoma (mucoepidermoid and adenoid cystic), primary lymphoma

Imaging Findings

FDG PET overall sensitivity for all NET approximately 76%
MCC
- FDG PET usually shows intense uptake within primary and metastatic lesions for MCC
For non-MCC NET, FDG may show variability
Some head and neck NET may show very little FDG activity
Salivary
- PET: Sensitivity and specificity 75% and 67%
- 30% false positive rate for malignancy (mostly due to Warthin tumor)
PET/CT may be used to find primary in NSCCHN metastases

Top Differential Diagnoses

Metastatic Disease from Small Cell Carcinoma of the Lung
Benign Mixed Tumor or Pleomorphic Adenoma
Warthin Tumor
Parotid Metastases

Coronal PET (A), axial CT (B) and fused PET/CT (C) demonstrate a focal area of intense activity in the left neck

, corresponding to a Warthin tumor in the posterior left parotid.

Axial fused PET/CT demonstrates a non-FDG-avid nasal neuroendocrine tumor

TERMINOLOGY

Abbreviations and Synonyms

Non-squamous cell cancer of the head and neck (NSCCHN)
Neuroendocrine tumors (NET), small cell undifferentiated carcinoma, Merkel cell carcinoma (MCC)
Benign mixed tumors (BMT) or pleomorphic adenoma; Warthin tumor; parotid carcinoma (mucoepidermoid and adenoid cystic), primary lymphoma

Definitions

Heterogeneous group of tumors of neuroendocrine origin
Merkel cells first described by Frederick Merkel in 1875
- Believed to be slow-acting mechanoreceptors in the basal layer of the epidermis
- Provide information about touch and hair movement
Tumors of the parotid and submandibular glands (salivary glands)

IMAGING FINDINGS

General Features

Best diagnostic clue
- MCC: Aggressive cutaneous mass
- NET: Mass involving the structures listed below
- Salivary: Negative Tc-99m pertechnetate and positive FDG PET
Location
- MCC: Sun-exposed skin (head and neck 50%), most common location periorbital area; about 40% occur along the extremities
  - MCC is thought to arise from hair follicles or dermal Merkel cells, although no definite evidence exists
- NET: Salivary glands, larynx, sinonasal cavity, upper esophagus, and oral cavity for non-MCC NET tumors
- Most salivary gland tumors arise within the parotid gland
- Most parotid gland tumors are benign
Size: Range in size from a few millimeters to several centimeters; average size < 2 cm

Morphology: MCC: Firm violaceous or reddish nodular papule or plaque ± ulceration

Imaging Recommendations

Best imaging tool
- CT scan with contrast or PET/CT with contrast
- FDG PET likely helpful in MCC; other head and neck NET may have less FDG activity
- FDG PET overall sensitivity for all NET approximately 76%
- FDG PET may influence management in up to 25% of patients
- Salivary: Combination FDG PET or PET/CT and salivary gland scintigraphy with Tc-99m pertechnetate
Protocol advice: IV contrast for CT; arms down for PET or PET/CT
Additional nuclear medicine imaging options
- Radiolabeled octreotide not well-evaluated for NET tumors of the head and neck; better for evaluation of NET outside the head and neck
Correlative imaging features
- CT findings
  - Primary lesion may show necrosis, enhancement, or mass effect for both MCC and non-MCC NET
  - Lymphadenopathy range 1.2-11 cm; mean 4.2 cm

Nuclear Medicine Findings

MCC
- FDG PET usually shows intense uptake within primary and metastatic lesions for MCC
  - Average SUV max in one study 10.4
  - Several case studies and small series showing most MCC to be intensely FDG avid; occasional false negative
  - PET useful for staging, assessing tumor response, and surveillance
- For non-MCC NET, FDG may show variability
  - Some head and neck NET may show very little FDG activity
  - Metastatic lesions may show photopenia compared to background normal activity
Salivary
- PET: Sensitivity and specificity 75% and 67%
  - 30% false positive rate for malignancy (mostly due to Warthin tumor)
  - High grade salivary tumors have been described as having wide range of maximum SUV values
  - In general, high grade salivary tumors have SUV greater than 5.0
  - Exception is adenoid cystic carcinoma, whose low SUV is attributed to slow growth
  - Normal salivary glands may have minimal to moderate uptake and diffuse asymmetric uptake
  - Mean SUV of normal parotid in one study was 1.9 ± 0.68
  - 76% of patients in one study had asymmetric uptake, attributed to normal variance or inflammation
  - Some asymmetric appearances may be due to artifact secondary to head movement between emission and transmission scans
  - Tilted head position can also create appearance of asymmetry
  - PET and PET/CT show low accuracy for distinguishing between benign and malignant tumors due to high uptake of benign tumors
  - Inability to distinguish low grade malignant tumors from benign disease may have little clinical impact
  - Patients with low grade salivary cancer appear to show good prognosis after conservative treatment, similar to patients with benign salivary tumors
- Overall major impact in clinical treatment planning is seen in 40% of patients
Staging
- PET/CT may be used to find primary in NSCCHN metastases
  - Most primaries are located in thorax, head/neck, abdomen
- In patients with high grade salivary cancer, PET/CT has been shown to
  - Significantly improve diagnostic accuracy for evaluating extent of tumor and tumor stages compared with CT alone
- Superior for detection of cervical lymph node mets, distant mets, and second primaries
- PET has been shown to have significant impact on management of patients with salivary gland cancers for initial staging and restaging
- PET/CT provided correct staging in 85% of cases vs. 62% with CT
- Whole-body scan superior to conventional imaging for detection of distant mets
Additional nuclear medicine options
- MCC: Octreotide scan using somatostatin analog tagged with indium-111 as tracer used to detect metastases
  - Limited in assessing uptake in organs with physiologic uptake of octreotide such as liver, kidneys, spleen
  - Liver is one of the main sites of metastasis for MCC
- Ga-67 scintigraphy: Sensitivity and specificity for differentiation of benign from malignant parotid masses 58% and 72% respectively
- F-DOPA PET also shows some variability in the uptake

CT Findings

Criteria for malignant cervical lymph nodes
- Presence of necrosis
- Peripheral fatty hilum
Morphologic imaging generally poor for differentiating benign from malignant parotid tumors
- Characteristics such as irregular margins and infiltration into parenchyma useful but not reliable