An introduction to head and neck pathology

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Head and neck pathology is squamous cell carcinoma and weird stuff. The thyroid is dealt with in its own article, as is pathology of the salivary gland.

Cytopathology of the head and neck is dealt with in a separate article called head and neck cytopathology.

Clinical

Common lesions:[1]

  • Leukoplakia.
    • Homogeneous.
    • Non-homogeneous.
  • Erythroplakia - more worrisome for cancer than leukoplakia.

Leukoplakia

Hairy leukoplakia is dealt with in a separate section.
The typical benign leukoplakia is dealt with in a separate section.

General

  • Non-specific clinical finding - may be benign or malignant.
  • Associated with tobacco use.[2]

Risk of malignancy:

  • In twos series ~13% were associated with an invasive lesion.[3][4]
  • Non-homogenous leukoplakia has a greater risk of malignancy than homogenous.[4]
  • Location matters - floor of mouth and ventral tongue lesions higher risk for malignancy.[5]

Gross

  • White lesion - may be subdivided:
    • Non-homogenous.
    • Homogenous.

Microscopic

Features:[1]

DDx:

Erythroplakia

General

  • Non-specific clinical finding - may be benign or malignant.
  • Strong association with non-keratinizing squamous lesions (invasive and dysplastic).

Microscopic

Features:[1]

  • Unidentified red lesion.
  • Often erosion.

Overview

Cysts

Larynx

Oral

Infectious:

Other:

Vascular:

Pigmentation:

Nasal cavity/nose

Benign cystic lesions

Cytology dealt with in Head and neck cytopathology.

Cystic lesions - overview

Lateral cystic lesions:

Medial cystic lesions:

Lateral & medial lesions:

Rathke cleft cyst

  • Arises from intermediate lobe - embryonic remnant.
  • Benign cystic lesion without calcification.
  • Related to craniopharyngioma.

Thyroglossal duct cyst

General

  • Congenital.
  • Midline.

Treatment:

  • Surgical excision (with piece of hyoid bone).

Microscopic

Features:

  • Cyst.
    • Lining:
      • Squamous or respiratory epithelium.
      • Cyst contents: debris.
  • +/-Thyroid gland.
  • +/-Granulomatous inflammation (phagocytosis of debris).

Images:

Sign out

No history provided

MASS, SUBMENTAL (MIDLINE), EXCISION:
- SQUAMOUS LINED CYST WITH EXTENSIVE DENUDATION AND, ACUTE AND CHRONIC INFLAMMATION.
- BENIGN SKELETAL MUSCLE.
- NEGATIVE FOR MALIGNANCY.

COMMENT:
No definite thyroid tissue is identified.  The findings may represent a thyroglossal 
duct cyst.

Branchial cleft cyst

  • AKA branchial cleft remnant.

General

  • Benign congenital thingy in the lateral neck.[8]
  • Most common cystic neck lesion in young adults.[9]
  • Treatment: excision.

Gross

  • Lateral neck mass.

Image - clinical:

Microscopic

Features:

  • Cystic space lined by squamous epithelium - usually.
    • +/-Inflammation.
  • Connective tissue:
    • +/-Adipose tissue.
    • +/-Cartilage.
    • +/-Bone.
    • +/-Muscle.

DDx:

Image:

IHC

Benign lymphoepithelial lesion

  • AKA benign lymphoepithelial cyst

General

  • Usually parotid gland.
  • Associated with autoimmune disease, e.g. Sjoegren disease, may not remain benign.[11]

Microscopic

Features:

  • Lymphocytes.
  • Ductal epithelial cells.[12]

Note:

IHC

  • CD20, CD3 -- mixed population.
  • Kappa ~ lambda.

Other benign

Vocal cord nodule

General

  • Benign.
  • AKA singer's nodule.
  • Etiology: overuse, mechanical trauma (?).

Microscopic

Features:[13]

  • Early:
    1. Edema.
    2. Fibroblasts proliferation.
  • Late:
    1. Subepithelial hyaline / stromal hyaline.
    2. Blood vessels - dilated.

Notes:

  • No inflammation.

DDx:[14]

Images:

Sign out

VOCAL CORD LESION, EXCISION:
- STRATIFIED SQUAMOUS EPITHELIUM WITH PARAKERATOSIS AND SUBEPITHELIAL 
  HYALINE MATERIAL, CONSISTENT WITH WITH VOCAL CORD NODULE OR POLYP.
- NEGATIVE FOR MALIGNANCY.

Squamous papilloma

Laryngeal papilloma redirects here.
Caruncle lesion is dealt with in papilloma of the caruncle.
The lesion in the esophagus is dealt with in squamous papilloma of the esophagus.

General

  • Benign.
  • Typically related to HPV 6 and HPV 11.

Gross

Features:[15]

  • Exophytic mass.

Microscopic

Features:[15]

  • Branching papillae.
    • Papilla = nipple-like projection with a fibrovascular core.
  • Basal cell hyperplasia.
  • Koilocytes.

Note:

DDx:

Images:

Sign out

LARYNGEAL LESION ("LARYNGEAL PAPILLOMA"), RIGHT, BIOPSY:
- SQUAMOUS PAPILLOMA.

Not definite

TONGUE PAPULE, RIGHT, BIOPSY:
- SQUAMOUS EPITHELIUM WITH PARAKERATOSIS AND VERY SCANT STROMA WITH FEATURES
SUGGESTIVE OF A SQUAMOUS PAPILLOMA.
- NEGATIVE FOR DYSPLASIA AND NEGATIVE FOR MALIGNANCY.

Dysplastic

LARYNGEAL LESION ("LARYNGEAL PAPILLOMA"), LEFT, BIOPSY:
- SQUAMOUS PAPILLOMA WITH LOW-GRADE DYSPLASIA.
- NEGATIVE FOR HIGH-GRADE DYSPLASIA AND NEGATIVE FOR MALIGNANCY.
- CLOSE FOLLOW-UP IS RECOMMENDED.

Micro

The sections show fibrovascular cores covered by stratified squamous epithelium with basal cell hyperplasia and edema. Scattered lymphocytes are present in the epithelium. No mitotic activity is appreciated. There is no significant nuclear atypia. Dyskeratotic cells are seen focally. Parakeratosis is present. Koilocytes are not apparent.

Low-grade dysplasia

The sections show fibrovascular cores covered by stratified squamous epithelium. Scattered lymphocytes are present in the epithelium. Rare mitotic activity is appreciated in the lower third of the epithelium. Mild nuclear atypia (hyperchromasia and mild nuclear enlargement in the lower third of the epithelium) is present. Dyskeratotic cells are seen focally. Parakeratosis is present. Koilocytes are seen focally.

Pemphigus vulgaris

General

  • May lead to blindness.
  • Oral lesion is classically: first to show & last to go.
    • Oral lesions usually precede the skin lesions.

Etiology:

  • Autoimmune disease.
    • Antibodies against: desmoglein 1, desmoglein 3.

Microscopic

Features:[18]

  • Suprabasilar blistering.

DDx: Hailey-Hailey disease.

Pyogenic granuloma

  • AKA lobular capillary hemangioma.[19]

General

  • Sometimes pregnancy tumour.
  • Seen in children, young adults, pregnant women.

Clinical:

  • May grow quickly - clinically suspicious for a malignancy.

Notes:

Gross

Features:[21]

  • Erythematous.
  • Hemorrhagic.

Usually location:[20]

Microscopic

Features:[22]

  • Polypoid or peduculated.
  • Vascular, i.e. many blood vessels, with plump endothelium.
  • Usu. thinned epithelium[23] or ulcerated.[20]
  • Lobular arrangement of vascular (seen at low power).[24]

DDx:

Why it is not...

Image

www:

IHC

Features - positive for vascular markers:[20]

  • CD34 +ve.
  • CD31 +ve.
  • Factor VIII +ve.

Sign out

TONGUE, LEFT LATERAL, BIOPSY:
- LOBULAR CAPILLARY HEMANGIOMA (PYOGENIC GRANULOMA).

Micro

The sections shows a pendunculated vascular lesion with small capillaries arranged in a lobular fashion. The endothelial cells of the lesion show no atypia. The overlying acanthotic epidermis has hyperkeratosis and hypergranulosis, and is focally ulcerated and impetiginized. There is no significant keratocyte atypia. No melanocytic nests are seen. The dermis has a mild perivascular lymphoplasmacytic infiltrate. The lesion is excised in the plane of section.

Plummer-Vinson syndrome

Triad:[21]

  • Iron-deficiency anemia.
  • Glossitis.
  • Esophageal dysphagia (usually related to webs).

Rhinoscleroma

General

  • Caused by Klebsiella rhinoscleromatis.
  • Nose involved +95% of the time.[26]

Gross

  • Nasal mass - may be deforming.

Image:

Microscopic

Features:[27]

  • Macrophages - clear-to-foamy cytoplasm.
  • Lymphocytes.
  • Plasma cells.

DDx:

Images:

Stains

  • Warthin-Starry stain +ve (rod-shaped organisms).
  • Dieterle stain +ve (rod-shaped organisms).

Neoplasms

Odontogenic tumours and cysts

This is a rather large topic and dealt with in a separate article.

It includes:

Pharyngeal/nasopharyngeal specimens

  • Specimens may be challenging to interpret as there is normally an abundance of lymphoid cells.
  • Malignant tissue can look benign.[29]
  • May be difficult to differentiate from other malignancies.

Histology

  • Upper airway distant from areas with friction: respiratory type epithelium.

Work-up of negative H&E Bx differs by site:

Laryngeal neoplasms

These are dealt with in a separate article.

Human papillomavirus-associated head and neck squamous cell carcinoma

  • Abbreviated HPV-HNSCC.

General

  • Tumours associated with high risk HPV, typically HPV 16.[31]
    • Thought to be different that tumours driven by alcohol and tobacco use.[32]
      • Patients tend to be male and slightly younger - risk thought to be due to sexual practices.[33]
  • Lesions more radiosensitive and usually have a better prognosis.[31]

Gross

Classic locations:

  • Tonsil and base of tongue[34] (palatine tonsil, lingual tonsil, oropharynx).

Note:

  • Memory device:
    • Where the tip of the penis goes when someone is deep throating.

Microscopic

Features:[35]

  • Typically non-keratinizing squamous cell carcinoma.

DDx:

  • HPV-negative squamous cell carcinoma.

Images:

IHC

  • p16 +ve.[34]
  • EBER -ve.

Sinonasal undifferentiated carcinoma

  • Abbreviated SNUC

General

  • Aggressive/poor prognosis.
    • In the past, survival was measured in months.[36]
    • With (aggressive) combined modality treatment, the overall five-year survival is approximately 75%.[37]

Microscopic

Features:[38]

  • Architecture: nested, trabecular or lobular.
  • Distinct cellular borders.
  • Small-to-moderate cytoplasm.
  • +/-Distinct nucleoli.
  • Tumour cell size variable (small to large).

Note:

  • Glandular and squamous differentiation are absent by definition.[39]

Images:

IHC

Features:[38]

  • Pankeratin +ve.
  • EMA +ve.
  • CK7 +ve.
  • CK5/6 -ve.

Others:

  • NSE +ve/-ve.
  • Chromogranin A -ve.
  • Synaptophysin -ve.
  • p63 +ve/-ve.[40]

Nasopharyngeal carcinoma

  • Abbreviated NPC.

General

  • "Nasopharyngeal carcinoma" is the name of an entity - it is not a descriptive term.
  • Strong association with Epstein-Barr virus (EBV).

Note:

Gross

  • Nasopharynx - as the name would suggest.

Microscopic

Features:[41]

  • Prominent lymphoid component - key feature.
  • Features of squamous cell carcinoma:
    • Cohesive cells with:
      • Abundant dense eosinophilic cytoplasm.
      • Central nuclei +/- small/indistinct nucleoli.

Images:

Histologic subclassification

World Health Classification (2005) for NPC:[42]

Type Histology Description EBV Prevalence Prognosis
1 keratinizing SCC graded poorly-well-diff. -ve ? bad
2a nonkeratinizing carcinoma, differentiated well def. cell borders & tumour nest borders, mimics appearance of UCC +ve ? good
2b nonkeratinizing carcinoma, undifferentiated sheets/syncytial, vescicular nuclei, prominent nucleoli, pink cytoplasm ? most common ?
3 basaloid SCC mimics BCC - see basaloid SCC ? least common ?

How to remember KNUB:

  • Keratinizing, Non-keratinizing diff., non-keratinizing Undiff., Basaloid SCC.

IHC

  • EBER +ve.
  • p16 -ve.[43]

Notes:

Squamous lesions

  • Premalignant lesions
    • Mild dysplasia.
      • Low risk of progression to invasive lesions.
    • Moderate dysplasia.
    • Severe dysplasia/carcinoma in situ (CIS).
      • Histologically severe dysplasia and CIS cannot be differentiated reliably; ergo, there can be considered the same thing.
      • Severe dysplasia is not a necessary intermediate for cancer, i.e. invasive squamous cell carcinoma may be present with moderate dysplasia.
  • Invasive squamous cell carcinoma (SCC).
    • "Microinvasive" squamous cell carcinoma - term should be avoided as there is no concenus on what it means.
    • There are several subtypes of SCC.

Squamous dysplasia of the head and neck

General

  • Similar to squamous dysplasia elsewhere.

Sign out

PHARYNGEAL WALL, POSTERIOR, BIOPSY:
- SQUAMOUS MUCOSA WITH MILD SQUAMOUS DYSPLASIA.
- NEGATIVE FOR MALIGNANCY.

Squamous cell carcinoma of the head and neck

General

  • Most common malignant tumour of the head & neck.
  • Most common spindle cell tumour of the head & neck.

Microscopic

Classification

SCC is subdivided by the WHO into:[45]

  • Keratinizing type (KT).
    • Worst prognosis.
  • Undifferentiated type (UT).
    • Intermediate prognosis.
    • EBV association.
  • Nonkeratinizing type (NT).
    • Good prognosis.
    • EBV association.

Features based on classification:[45]

  • KT subtype:
    • Keratinization & intercellular bridges through-out most of the malignant lesion.
  • UT:
    • Non-distinct borders/syncytial pattern.
    • Nucleoli.
  • NT:
    • Well-defined cell borders.

Invasion

Features:

  • Eosinophilia.
  • Extra large nuclei/bizarre nuclei.
  • Inflammation (lymphocytes, plasma cells).
  • Long rete ridges.
  • Numerous beeds/blobs of epithelial cells that seem unlikely to be rete ridges.

Pitfalls:

  • Tangential cuts.
    • If you can trace the squamous cells from a gland to the surface it is less likely to be invasive cancer.

Notes on invasion:

Image(s):

Overview of subtypes

There are several subtypes:[47]

  • Basaloid - poor prognosis, usu. diagnosed by recognition of typical SCC.
  • Warty (Condylomatous).
  • Verrucous - good prognosis, rare.
  • Papillary.
  • Lymphoepithelial, rare.
  • Spindle cell, a common spindle cell lesion of the H&N.

Verrucous squamous cell carcinoma

Features:

  • Exophytic growth.
  • Well-differentiated.
  • "Glassy" appearance.
  • Pushing border.

DDx: papilloma.

Spindle cell squamous carcinoma

  • Key to diagnosis is finding a component of conventional squamous cell carcinoma.

IHC:

  • Typically keratin -ve.
  • p63 +ve.

DDx:

  • Spindle cell melanoma.
  • Mesenchymal neoplasm.

Basaloid squamous cell carcinoma

Features:

  • Need keratinization. (???)

DDx:

  • Neuroendocrine tumour.

Lymphoepithelial (squamous cell) carcinoma

  • Rare.
  • +/-EBV.

Small cell anaplastic carcinoma

  • Rare.

DDx:

Granular cell tumour

General

  • May mimic (well-differentiated) squamous cell carcinoma - histopathologically.
  • Usually a benign tumour.

Microscopic

Features:

  • Large polygonal cells with abundant (eosinophilic) granular cytoplasm.

Image:

Olfactory neuroblastoma

See also: neuroblastoma.
  • AKA esthesioneuroblastoma.

General

Epidemiology:[50]

  • Prognosis: poor.
  • Wide age range with bimodal distribution - teens and 60s.
  • No sex predilection.

Clinical presentation:[50]

  • Nasal obstruction ~ 70%.
  • Epistaxis ~ 50%.
  • Anosmia.
  • Headache.

Gross

  • Arises from olfactory mucosa - upper nasal cavity.[51]

Microscopic

Features:[50]

DDx:

Images:

IHC

  • S100:
    • Sustentacular cells +ve.
    • Small round cells -ve.
  • Neuroendocrine markers +ve (CD56, synaptophysin).

Others:

  • CD45 -ve (r/o lymphoma).
  • AE1/AE3 usu. -ve (r/o carcinoma).
  • CAM5.2 usu. -ve -- up to 35% +ve.[51]

Craniopharyngioma

  • Cystic lesion +/- calcifications +/-squamous nests.
  • Related to Rathke cleft cyst.

Nasopharyngeal angiofibroma

See also: Angiofibroma.
  • AKA juvenile nasopharyngeal angiofibroma.

General

  • Classically adolescent males with recurrent nose bleeds.

Microscopic

Features:[53]

  • Fibroblastic cells with plump (near cuboidal) nuclei.
  • Fibrous stroma.
  • Abundant capillaries.

Images:

Nasal polyps

Overview

DDx (benign - multiple):[54]

Memory devices:

  • GAIT = Genetic, Allergic/idiopathic, Infectious, Tumours.
  • Allergic causes As - allergic, asthma, allergic granulomatous angiitis (Churg-Strauss syndrome), nonallergic rhinitis with eosinophilia.

Epidemiology

  • More commonly assoc. with nonallergic conditions.[54]

Treatment

  • Recurrent polyps: functional endoscopic sinus surgery (FESS).

Inflammatory polyps with neutrophils

General

  • Histologic findings are non-specific; DDx includes:[56]

Microscopic

Features:

  • Neutrophil predominant.
  • Edema.
  • +/-Mucus-impaction (dilated glands with mucus).
    • Suggestive of cystic fibrosis.[57]

Sign out

A. Nasal sinus tissue, right, excision:
- Inflamed edematous sinonasal mucosa with abundant neutrophils.
- Negative for malignancy.

B. Nasal sinus tissue, left, excision:
- Inflamed edematous sinonasal mucosa with abundant neutrophils and fragments of bone.
- Negative for malignancy.

Allergic nasal polyp

General

  • People with allergies.
    • Same type of polyps seen in those without allergies.[58]

Gross

  • Polypoid mass - several millimetres to centimetres in size.

Microscopic

Features:[59]

  • Normal respiratory epithelium.
  • Stroma with:
    • Edema.
    • Eosinophils.
    • +/-Other inflammatory cells (plasma cells, lymphocytes, neutrophils).

DDx:

Sign out

A. Nasal sinus tissue, right, excision:
- Inflamed edematous sinonasal mucosa with abundant eosinophils.
- Negative for malignancy.

B. Nasal sinus tissue, left, excision:
- Inflamed edematous sinonasal mucosa with abundant eosinophils and fragments of bone.
- Negative for malignancy.


A. NASAL SINUS TISSUE, RIGHT, EXCISION:
- INFLAMED EDEMATOUS SINONASAL MUCOSA WITH ABUNDANT EOSINOPHILS.
- NEGATIVE FOR MALIGNANCY.

B. NASAL SINUS TISSUE, LEFT, EXCISION:
- INFLAMED EDEMATOUS SINONASAL MUCOSA WITH ABUNDANT EOSINOPHILS AND FRAGMENTS OF BONE.
- NEGATIVE FOR MALIGNANCY.

Tonsillar lymphangiomatous polyp

Microscopic

Features:[60]

  • Polyp with lymph channels.

Schneiderian papilloma

  • AKA Schneiderian polyp.
  • AKA sinonasal papilloma.[61]

General

  • Lumpers vs. splitters debate about whether it is one entity or three.[62]

Subclassification:[62]

  • Inverted (Schneiderian) - most common ~60-65%.
  • Fungiform (Schneiderian) - less common ~30-35%.
  • Oncocytic (Schneiderian) - least common ~5%.

Inverted

Fungiform

  • AKA exophytic papilloma, AKA septal papilloma.[62]
  • Low risk of malignant transformation.

Oncocytic

  • AKA cylindrical cell papilloma.[64]
  • Lateral nasal wall.[62]

Microscopic

Inverted Schneiderian papilloma

Features:[62]

  • Well-demarcated epithelial islands in the stroma.
  • Squamous +/-surface keratinization or respiratory type epithelium (with cilia).
  • +/-Neutrophils.
  • +/-Goblet cells.

Notes:

  • May mimic invasive SCC.

Images:

Fungiform Schneiderian papilloma

Features:

  • Exophytic growth pattern - key feature.

Oncocytic Schneiderian papilloma

Features:

  • Oncocytes - key feature.
  • Exophytic or endophytic growth pattern.

See also

References

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