SCCa, Unknown Primary Site

Deborah R. Shatzkes, MD

Key Facts

Terminology

SCCa in cervical lymph node with clinically occult primary site
Carcinoma of unknown primary (CUP)

Imaging

CECT or MR first-line imaging tool
- PET/CT may be helpful if this imaging negative
If primary site discovered, most often tonsil, tongue base, nasopharynx, or pyriform sinus apex
- Cystic lymph nodes → think oropharynx
Primary tumor may be predicted from site of nodes
- Parotid nodes from periauricular/facial skin SCCa
- Posterior triangle nodes from scalp SCCa
- Supraclavicular nodes from chest or abdomen SCCa

Top Differential Diagnoses

2nd branchial cleft cyst
Nodal differentiated thyroid carcinoma

Pathology

Nodal tissue tested for HPV/p16 and EBV markers, suggesting oropharyngeal and nasopharyngeal tumor, respectively

Clinical Issues

Neck mass → FNA yields SCCa → office exam negative → imaging → panendoscopy + directed biopsies
Identification of primary tumor site can reduce morbidity and mortality by allowing targeted radiation therapy

Diagnostic Checklist

Understanding nodal drainage pathways helps direct interrogation for primary site
View asymmetry in most common primary sites with extreme suspicion
HPV/p16(+) &/or cystic nodes suggests oropharynx!

(Left) Clinical photograph shows prominent nodal swelling in left neck

. (Right) Axial T1WI C+ FS MR in the same patient shows symmetric palatine tonsils

and no evidence of mass at tongue base

or elsewhere in pharynx and larynx. PET/CT (not shown) revealed uptake in enlarged nodes only. Multiple biopsies showed no primary tumor site. Repeat triple endoscopy showed subtle left base of tongue irregularity, which on final pathology revealed SCCa. Tumor truly is imaging occult.

(Left) Axial CECT shows cystic nodal mass in right level III

. Patient underwent endoscopic biopsies of nasopharynx, tongue base, and right pyriform sinus as well as right tonsillectomy. Pathology revealed the primary HPV(+) neoplasm in right tongue base. (Right) Axial CECT at level of tongue base

in same patient shows no suspicious mass or soft tissue asymmetry even in retrospect. HPV(+) oropharyngeal primaries are notorious for being small yet producing large cystic lymph nodes.

TERMINOLOGY

Synonyms

Carcinoma of unknown primary (CUP)
Primary unknown cervical lymph node metastasis (PUCLNM)

Definitions

SCCa in cervical lymph node with unknown primary site after clinical examination

IMAGING

General Features

Location
- If primary site is discovered, most often tonsil, tongue base, nasopharynx, pyriform sinus apex
  - Deep palatine and lingual tonsillar crypts may harbor small foci of SCCa
  - Fossa of Rosenmüller (nasopharynx) & pyriform sinus apex (hypopharynx) difficult to assess by office exam
- Location of primary can sometimes be predicted from site of adenopathy
  - Parotid nodes from periauricular/facial skin SCCa
    - Skin primaries may have been previously resected, and neither clinically evident nor reported in patient history
  - Suboccipital nodes from scalp SCCa
  - Isolated supraclavicular node (“Virchow node”) from infraclavicular primary
    - Chest, breast, or abdominal/pelvic primary site
    - More common on left when primary is abdominal/pelvic

CT Findings

CECT
- Solid or cystic nodal metastasis in neck
  - Most often found at level II
- Must search for subtle fullness, increased enhancement, or asymmetry of pharyngeal mucosa