Neoplasms of the Larynx and Trachea

Clinical

• Divided into:

  • Lesions that occur in early years referred to as juvenile-onset recurrent respiratory papillomatosis (JO-RRP)

  • Lesions that occur in older ages referred to as adult-onset recurrent respiratory papillomatosis (AO-RRP)

    • –

      Age separating juvenile versus adult onset not established and different studies cite different ages

    • –

      Although not universally accepted, 20 years of age can serve as a potential dividing line between JO-RRP and AO-RRP.

Pathology

Differential Diagnosis

• Verruca vulgaris:

  • Typically occurs in cutaneous sites

  • Infrequently occurs in mucosal sites, including lips

  • Etiologically linked to HPV:

    • –

      HPV 2 and 4 typically associated with VV of the skin, lips, and oral cavity

    • –

      HPV 6 and 11 identified in laryngeal VV

  • Rare lesion of the larynx:

    • –

      Much more common in men than in women; disease of adults

    • –

      Most common on the true vocal cord

    • –

      Hoarseness is the most common symptom.

  • Exophytic, demarcated warty-appearing white lesion usually measuring less than 1 cm

  • Histologically similar to verruca vulgaris of the skin and includes:

    • –

      Verrucoid appearance

    • –

      Keratosis

    • –

      Prominent granular cell layer

    • –

      Coarse and irregular keratohyaline granules

    • –

      Thin, pointy rete pegs

    • –

      Presence of koilocytes

  • Simple excision is curative.

  • Recurrence may rarely occur.

• Verrucous carcinoma

• Papillary or exophytic squamous cell carcinoma

Treatment and Prognosis

• Because of the unpredictable nature of disease, which may be characterized by periods of active growth and remission, best mode of treatment and the efficacy of treatment remain uncertain:

  • Presently recommended treatment for RRP is surgery, including microlaryngeal excision with CO ₂ laser surgery

  • Adjunctive drugs used in treatment with varying success include interferon, various virostatics (e.g., acyclovir, valacyclovir, and cidofovir), and indole-3-carbinol

  • Vaccination with a quadrivalent vaccine against HPV types involved most commonly in RRP may provide the best hope to prevent severe forms of this disease.

• In general, treatment should be as conservative as possible with the primary aims of therapy to include:

  • Airway maintenance

  • Voice preservation

  • Reduction of tumor burden with the goal of disease eradication

  • Avoidance of tracheotomy:

    • –

      Tracheotomy may be required to maintain a functional airway in as high as 65% of patients.

    • –

      On average tracheotomy is required in approximately one third of patients.

    • –

      If tracheotomy is required, then the maintenance of airway patency and use of the shortest tracheotomy tube are advised.

• Complications of surgery may include:

  • Laryngoceles

  • Scarring

  • Stenosis

  • Arytenoid fixation

• Radiotherapy is contraindicated because of its associated complications, including:

  • Laryngeal destruction, scarring, and laryngeal stenosis and the risk of inducing malignant transformation

  • 16-fold increased risk of developing carcinoma in patients who have been irradiated

• Recurrence of tumor is common, requiring long-term and repeated management:

  • Recurrence correlates with persistence of HPV.

  • HPV can be identified in nonpapillomatosis mucosa adjacent to the papilloma in as many as 75% of patients:

    • –

      Identification of HPV in nondiseased mucosa by in situ hybridization and polymerase chain reaction

• Variability of disease course is reflected in the unpredictable nature of recurrent tumor:

  • Some patients experience one or two recurrences over a few-year period followed by spontaneous remission.

  • Other patients have frequent recurrences over very short periods of time (weeks), necessitating multiple operative procedures.

  • Other patients may have repeated recurrences over short periods of time and then remain disease free for decades only to have multiple recurrent diseases later in life, necessitating multiple operative procedures.

  • Appears that patients with RRP are at risk throughout their lives for the possibility of local recurrence

  • In approximately 80% of patients disease persists for 5 years or longer.

  • Effect of puberty and pregnancy on the course of disease remains controversial:

    • –

      In some patients the disease resolves or becomes less aggressive in puberty or pregnancy.

    • –

      In some patients the disease progresses/becomes more aggressive in puberty or during pregnancy.

• Overall mortality rate varies from 2% to 14%:

  • Extension into the tracheobronchial tree occurs in 2% to 15% and involvement of lower respiratory tract parenchyma is associated with increased mortality rates.

  • Death may be caused by asphyxiation, superimposed infection, and malignant transformation.

• Carcinoma developing in RRP may occur in nonirradiated and in irradiated patients:

  • Overall incidence of developing carcinoma in nonirradiated patients is 2%.

  • Overall incidence of developing carcinoma in irradiated patients is 14%.

  • Carcinoma developing in the setting of RRP is squamous cell carcinoma.

  • Transformation of RRP to squamous cell carcinoma may:

    • –

      Be spontaneous, not characterized by histologic progression, through dysplasia over time

    • –

      Develop through a continuum of dysplasia over time

  • Transformation to squamous cell carcinoma may result in loss of HPV expression.

  • Carcinoma developing in RRP may develop in larynx or in the lung.

  • Laryngeal carcinomas developing spontaneously (i.e., in nonirradiated patients) tend to:

    • –

      Occur in JO-RRP

    • –

      Develop decades after disease onset

    • –

      Have lower mortality rates

  • Laryngeal carcinomas developing in irradiated patients tend to:

    • –

      Occur in JO-RRP

    • –

      Develop in shorter interval periods (decade or less) after disease onset

    • –

      Have higher mortality rates

  • Lung carcinomas developing in nonirradiated and nonsmoking patients tend to:

    • –

      Have early onset of RRP ranging in age from 1 to 6 years with an average age of onset of years

    • –

      Have disease extension down the tracheobronchial tree into the lungs

    • –

      Develop carcinoma approximately 25 years after laryngeal disease

    • –

      Often have metastatic disease (regional lymph nodes and distant)

    • –

      Have high mortality rates usually over short periods of time following the diagnosis of carcinoma

  • Factors in RRP reported to be associated with increased risk of aggressive behavior with spread to lower airway passages, malignant transformation, and death include:

    • –

      Patients with HPV type 11:

      • ▪

        Malignant transformation reported solely for HPV 11–associated RRP in 2% to 4% of all RRP cases

      • ▪

        Malignant transformation not reported to be associated with HPV 6; however, a patient with HPV 6 expressing E6 and E7 oncogenes shown to follow similar aggressive clinical course as patients with HPV 11

        • □

          These patients developed disease at a younger age and expressed higher levels of E6 and E7 oncogenes compared with the patients with more indolent course.

    • –

      Alterations of aldo-keto reductase 1C3 gene (AKR1C3) on chromosome 10p15.1 may be implicated in carcinogenesis.

    • –

      Severity score of greater than 4:

      • ▪

        Includes functional assessment of clinical parameters and an anatomic assessment of disease distribution

      • ▪

        Anatomic score can then be used in combination with the functional score to measure an individual patient's clinical course and response to the therapy over time.

    • –

      A high number of surgical procedures prior to interferon-alpha therapy

Clinical

• No gender predilection; disease of adults but may occur over a wide age range, including patients younger than 50 years of age

• Tend to occur on the true vocal cord

• Patients usually present with hoarseness.

• Cause:

  • Not etiologically linked to human papillomavirus (unlike nonkeratinizing papillomas)

  • Reported to occur in patients with smoking history

Pathology

Differential Diagnosis

• Verrucous carcinoma

• Papillary or exophytic squamous cell carcinoma

Treatment and Prognosis

• Surgical resection is usually curative.

• Usually do not recur but occasionally may recur

• Rarely undergo malignant transformation to a carcinoma

Clinical

• IMT of upper aerodigestive tract are rare:

  • Aside from scattered case reports there are very few comprehensive studies detailing the clinicopathologic features of IMT in upper aerodigestive tract sites.

• Male predominance; contrasting to soft tissue and visceral IMT, which occur predominantly in children and young adults, IMT of the upper aerodigestive tract occur over a wide age range that includes the pediatric population but is more common in adult populations:

  • Relative to laryngeal IMT, median age of 59 years reported

• In upper aerodigestive tract, IMT most commonly occur in the larynx:

  • Laryngeal sites of involvement include glottis, supraglottis, and subglottis.

  • Most common site of occurrence is the true vocal cord

  • Nonlaryngeal sites of occurrence include oral cavity, tonsil, parapharyngeal space, sinonasal tract, salivary glands, and trachea.

• Clinical presentation varies per site of occurrence:

  • Larynx: hoarseness, stridor, dysphonia, and/or a foreign body sensation in the throat; duration of symptoms range from as short as 10 days up to 4 months

  • Other aerodigestive tract sites may present as painless mass, ulcerative painful mass, nasal obstruction, epistaxis, headaches, and dysphagia.

  • Constitutional and/or systemic signs and symptoms such as fever, weight loss, pain, malaise, anemia, thrombocytosis, polyclonal hyperglobulinemia, and elevated erythrocyte sedimentation rate seen in association with soft tissue and visceral IMT are not usually a component of upper aerodigestive tract IMT. High fever, anemia and weight loss may be present.

• IMT of the upper aerodigestive tract present as solitary (isolated) lesions, typically without lesions of other upper aerodigestive tract sites or evidence of myofibroblastic lesions of other sites of the body.

• Cause of IMT in general and upper aerodigestive tract in specific is unknown:

  • No specific link to tobacco smoking, trauma (e.g., traumatic intubation), human herpesvirus-8 (HHV-8), or Epstein-Barr virus (EBV)

Pathology

Differential Diagnosis

• Contact ulcer of the larynx

• Pyogenic granuloma

• Nodular fasciitis:

  • Myofibroblastic dominant proliferation

  • Typically a lesion of soft tissue but rarely may be mucosal based, originating in mucosal sites of upper aerodigestive tract, including the larynx and pharynx

  • For a more complete discussion, see Section 4, Neck.

• IgG4-related disease:

  • Although there may be some overlap in histologic findings and presence of increase IgG4 plasma cells between IgG4-related disease and IMT, these two entities have distinct clinical and pathologic findings:

    • –

      IgG4-related disease is typically systemic but may be localized, whereas IMT are generally localized.

    • –

      Histologic findings often seen in IgG4-related disease include obliterative phlebitis and lymphoid aggregates, features not seen in IMT.

    • –

      IgG4-related disease is ALK negative.

    • –

      IgG4-related disease responds to steroid treatment.

  • For a more complete discussion of IgG4-related disease see Section 6, Salivary Glands.

• Spindle cell squamous carcinoma:

  • Overtly malignant cell infiltrate that may be associated with intraepithelial dysplasia and/or invasive squamous cell carcinoma

  • Reactivity may be seen for epithelial markers (cytokeratins, others) and p63.

  • Consistently reactive for vimentin and may be reactive for mesenchymal markers including actins and desmin

  • ALK negative

  • Spindle cell squamous carcinomas, especially those with associated surface ulceration and reactive changes, may have coexisting (reactive) myofibroblasts, the latter representing part of the wound healing process.

• Myofibrosarcoma

Treatment and Prognosis

• Laryngeal IMT are treated by conservative surgical resection, including local excision by laser removal or via laryngoscopic techniques.

• Conservative resection usually curative:

  • Rarely, recurrent tumor may occur after con­servative surgical resection necessitating laryngectomy.

• Targeted therapy using ALK inhibitor crizotinib has shown promising results in ALK-translocated IMT

• Recurrence rate of approximately 25% has been reported for extrapulmonary IMT.

• Rare examples of extrapulmonary (not head and neck) IMT metastasize (less than 2%):

  • May be linked to presence of RANBP2 and round cell morphology

  • ALK-negative IMT may have higher risk of metastasis.

• Difficult to predict on the basis of pathologic features which IMTs may behave more aggressively:

  • No correlation between behavior and tumor size, nuclear atypia, mitotic activity, necrosis

  • Aggressive behavior may correlate to round cell transformation characterized by:

    • –

      Sheets of round to epithelioid cells with vesicular nuclei, prominent nucleoli, amphophilic to eosinophilic cytoplasm, increased mitotic activity including atypical mitoses, myxoid stroma, and prominent neutrophilic infiltrate

    • –

      Distinct nuclear membrane or perinuclear pattern of ALK staining

    • –

      RANBP2-ALK fusion detected by reverse transcription polymerase chain reaction

    • –

      To date, such changes reported in IMT located within the abdomen arising from omentum or mesentery

    • –

      Terminology of epithelioid inflammatory myofibroblastic sarcoma suggested for this lesion conveying malignant behavior

Clinical

• Can occur in virtually any organ but most frequent sites of occurrence include:

  • Skin > tongue > breast > larynx > gastrointestinal tract > bronchus, trachea

  • Except for the larynx, granular cell tumors are more common in women than in men

  • See Section 2 on the Oral Cavity for a discussion of lingual granular cell tumor and congenital granular cell epulis.

• For laryngeal tumors:

  • No gender predilection; primarily affects adults in third to fifth decades of life; uncommon in children

  • Hoarseness is most common complaint.

  • Most frequently identified along the posterior aspect of the true vocal cord (posterior one third) but can also be seen in the supraglottic and subglottic areas:

    • –

      Vocal cord > arytenoids > false cord > anterior commissure > subglottis > postcricoid area

• For tracheal tumors:

  • More common in women than in men

  • Wide age range but peak incidence is in the fourth decade

  • Symptoms include stridor and airway obstruction.

  • Most often arise in the cervical trachea

• Regardless of site, most GCTs are single lesions but multiple tumors may be found:

  • May occur synchronously or metachronously

  • Multiple granular cell tumors may occur in LEOPARD syndrome and Noonan syndrome associated with mutations in PTPN11 .

• No known cause

• Granular cell tumors felt to be of neural (Schwann cells) origin supported by:

  • Involvement of small to medium nerves

  • S100 protein, CD57, and neuron-specific enolase positive

  • Presence of myelinated and nonmyelinated axon-like structures by ultrastructural analysis

  • Presence of residual axons in many granular cell tumors

Pathology

Differential Diagnosis

• Rhabdomyoma

• Invasive squamous cell carcinoma as a result of the PEH

• Alveolar soft part sarcoma

• Malignant granular cell tumor:

  • Rare neoplasms accounting for approximately 1% of all granular cell tumors

  • Clinically are similar to benign granular cell tumors except that they do not occur in newborns or children

  • Usually measure >4.0 cm in diameter and tend to occur in the extremities

  • Histologically, a diagnosis of malignancy can be made in the presence of three of the following criteria:

    • –

      Necrosis

    • –

      Spindle-shaped cells

    • –

      Increased nuclear-to-cytoplasmic ratio

    • –

      Vesicular nuclei with prominent nucleoli

    • –

      Pleomorphism

    • –

      Increased mitotic activity (greater than two mitoses per 10 high-power fields)

  • Any granular cell tumor in which one or two of the above criteria are found can be referred to as atypical.

  • Transition from benign granular cell tumor to malignant granular cell tumor is frequently apparent.

  • Immunohistochemical staining similar to that of benign granular cell tumors except:

    • –

      CEA reactivity reported, significance of which is not known

    • –

      Increase proliferation rate from 10% to 50% by Ki67 (MIB1) staining

    • –

      Extensive p53 staining in up to 70% of cases

  • Differential diagnosis includes alveolar soft part sarcoma and paraganglioma.

  • Surgery is the preferred treatment (wide en bloc excision); radio- and chemotherapy are ineffective.

  • Metastasize via lymphatics and blood vessels (lymph nodes, lung, liver, and bone)

Treatment and Prognosis

• Conservative but complete surgical excision is considered curative:

  • Small tumors can be excised endoscopically.

• Granular cell tumors are radioresistant.

• Local recurrence may occur in a minority of patients (less than 10%):

  • Recurrent tumor may represent a new primary lesion in patients with multifocal disease.

Histoanatomy

• Laryngeal paraganglia are microscopic structures with variable anatomic distribution in relation to cricoid and thyroid cartilages.

  • Most are paired structures located in superior and inferior locations in lateral larynx.

  • Sometimes found immediately adjacent to thyroid gland or within capsule of thyroid gland

  • Described in relation to laryngeal recurrent nerve

• Physiologic role of laryngeal paraganglia unknown

Clinical

• Uncommon laryngeal tumor

• More common in women than in men; wide age range but most common in the fifth decade of life

• Vast majority (greater than 80%) predilect to the supraglottic larynx with the aryepiglottic fold and false vocal cord representing the most common sites of occurrence.

• Clinical presentation includes hoarseness, dysphagia, dyspnea, and stridor.

• Generally are not hormonally (functionally) active, although exceptional cases may be functional.

• Rarely may be multicentric with other head and neck paragangliomas

• Radiology:

  • CT: enhancing mass

  • MRI: intermediate signal intensity on T1-weighted image and high signal intensity on T2-weighted image

Pathology

Differential Diagnosis

• Neuroendocrine carcinomas including carcinoid tumor and atypical carcinoid (see Box 16-5 and Table 16-6 )

Treatment and Prognosis

• Surgery is the preferred treatment and is curative.

• Malignant paragangliomas reported in the literature more likely represent neuroendocrine carcinoma

Clinical

• Cartilaginous neoplasms of the head and neck are uncommon, and those of the larynx are rare:

  • Laryngeal chondrosarcomas are more common than chondromas.

• Most common sites of occurrence of head and neck chondromas include:

  • Sinonasal tract

  • Less common sites include maxilla and mandible, larynx, palate, pharynx, nasopharynx, and ear.

• In the larynx, chondromas may originate from posterior lamina of cricoid cartilage and thyroid cartilage and less often from epiglottis and arytenoids.

  • May arise in soft tissues of the true vocal cords (Reinke space)

• May be incidentally identified or cause hoarseness:

  • A clinically significant cartilaginous tumor of the larynx is most likely a chondrosarcoma.

• Radiology:

  • Discrete soft tissue mass contiguous with its laryngeal cartilaginous origin

  • Coarse calcifications and ossification may be seen.

• Involvement of Reinke space most probably represents a metaplastic rather than a true neoplastic process with derivation from the vocal cord ligament.

Pathology

Differential Diagnosis

• Cartilaginous hamartoma

• Chondrosarcoma (see later in chapter)

Treatment and Prognosis

• Conservative but wide surgical excision including an adequate margin of normal tissue is the preferred treatment:

• Surgical resection is curative.

  • Recurrences are uncommon and according to most authorities do not occur in association with laryngeal chondromas.

  • Recurrent chondromas of the larynx should prompt a diagnosis of a low-grade chondrosarcoma.

Clinical

• In the head and neck, most often occur in the neck region (see Section 4, Neck, for more complete discussion)

• Rare tumor of larynx (and hypopharynx)

• More common in men than in women; adult ages usually sixth decade and older

• Solitary tumors often arising in the supraglottic larynx or project into the larynx from a hypopharyngeal mass:

  • Laryngeal sites of occurrence include aryepiglottic fold, vestibular fold, and epiglottis.

• Symptoms include dysphagia, dyspnea, acute airway obstruction, hoarseness, dysphonia, and a lump in the throat.

• Radiology:

  • CT scan: low attenuation mass:

    • –

      Adipose tissue is the only soft tissue that has a density less than water (zero or negative Hounsfield units) so that CT scan reveals extent of the mass and also its lipomatous nature.

• No known cause:

  • Rare cases reported in association with symmetric lipomatosis (Madelung disease or Launois-Bensaude syndrome)

Pathology

Differential Diagnosis

• For conventional lipoma:

  • Atypical lipomatous neoplasm/well-differentiated (lipoma-like) liposarcoma; see later in chapter.

• For myxoid lipoma:

  • Vocal cord polyp, myxoid type

  • Myxoid liposarcoma

• For spindle cell lipoma:

  • Various spindle cell neoplasms of these sites

Treatment and Prognosis

• Surgery is curative.

• May rarely recur:

  • May be a function of inadequate excision

  • Presence of recurrence should raise diagnosis of well-differentiated liposarcoma:

    • –

      Does not represent transformation from a lipoma but initial lesion was a liposarcoma that went undiagnosed due to overall bland morphology lacking overt evidence of malignancy

    • –

      In this setting staining for MDM2 and CDK4 may prove useful and diagnostic.

Clinical

• More common in men than in women; generally limited to the adult population with a mean age at diagnosis in the sixth decade of life

• May occur anywhere in the larynx but mainly identified along the true vocal cord:

  • Typically is a unilateral lesion but may be bilateral in up to 30% of cases

• Most frequent symptom is hoarseness.

• May appear white (leukoplakia), red (erythroplakia), or mixed red and white (speckled leukoplakia):

  • See Section 2, Oral Cavity, for more complete discussion on leukoplakic and erythroplakic lesions.

• Causes may include:

  • Tobacco smoking (most common) and excess alcohol use:

    • –

      Alcohol potentiates the effect of tobacco smoking.

    • –

      Risk of developing dysplastic lesions increases with duration of smoking and/or alcohol use.

  • Chronic infections, including fungal infection

  • Less commonly secondary to voice abuse, environmental/industrial exposure, and vitamin A deficiency

  • Role of human papillomavirus in development of intraepithelial dysplasia of the larynx remains unproven:

    • –

      High-risk HPV uncommon finding in head and neck squamous cell carcinoma from patients who have history of tobacco or alcohol use

    • –

      Low-risk HPV not associated with such cases

  • Prevalence of HPV in precursor lesions (i.e., dysplasia) reported in approximately 12% of cases

  • HPV DNA reported in 12% to 25% of normal (clinically and histologically) larynges

Pathology

Differential Diagnosis

• Reactive epithelial changes

• Infectious disease(s)

• Microinvasive carcinoma:

  • Diagnosis of microinvasive carcinoma should be reserved for cases in which there is definitive evidence of dissociated squamous cells at the epithelial-to-stromal interface with invasion of the lamina propria; see later in section for more complete discussion.

Treatment and Prognosis

• Excisional biopsy by vocal cord stripping or by forceps is preferred treatment.

• Close follow-up of the patient is advocated; if clinically warranted, rebiopsy may be necessary and should be performed months after any procedure to allow adequate healing and fewer surgery-associated pathologic changes that may hamper the histologic evaluation and/or obscure a neoplastic process.

• Cessation of contributing risk factors should be undertaken:

  • In general, mild and moderate dysplasias are felt to be potentially reversible alterations.

  • Circumstantial evidence supports the idea that preinvasive dysplasias are potentially reversible after cessation or removal of an instigating factor such as tobacco use.

  • Problem of predicting the malignant potential of a dysplastic lesion is greatest in cases of moderate dysplasia:

    • –

      Virtually impossible to differentiate the moderately dysplastic lesions that are reversible from those that represent the earliest forms of neoplastic transformation

    • –

      Diagnosis of moderate dysplasia should engender enough concern to the clinician to warrant close patient follow-up.

    • –

      Recurrence or persistence of this dysplasia may be indicative of malignant transformation.

    • –

      Determination of whether a mild to moderate dysplasia is reactive or neoplastic, although a desirable goal, is not always achievable; the clinically abnormal lesions that show limited cytologic and architectural abnormalities falling under the designation of reactive atypias or hyperplastic lesions represent reversible changes that rarely, if ever, progress to carcinoma:

      • ▪

        These lesions are responsive to conservative management.

    • –

      Uterine cervical moderate dysplasia (cervical intraepithelial neoplasia II) and severe dysplasia (cervical intraepithelial neoplasia III) are currently lumped in the category of high-grade squamous intraepithelial lesion (HGSIL).

    • –

      Risk of progression to invasive carcinoma relative to upper aerodigestive tract moderate dysplasia (approximately 23%) and severe dysplasia (approximately 28%) is not statistically significant.

    • –

      To date, grouping of upper aerodigestive tract keratinizing moderate and severe dysplasia into a single category as high-grade squamous intraepithelial lesion similar to the uterine cervix has not been adopted but may be the recommended grading scheme in the near future to include:

      • ▪

        Low-grade squamous intraepithelial lesion/neoplasia for mild dysplasia

      • ▪

        High-grade squamous intraepithelial lesion/neoplasia for moderate and severe dysplasias

Clinical

• Represents approximately 1% to 13% of all laryngeal carcinomas

• More common in men than in women; most frequently seen in the sixth to seventh decades of life

• Can occur anywhere in the larynx but most often involves the anterior one third of one or both true vocal cords:

  • May involve the entire cord

  • May be bilateral

  • Frequently associated with an invasive squamous cell carcinoma either lying adjacent to or remote from one another

  • May exist as an isolated lesion unrelated to invasive carcinoma

  • Multifocal areas can occur.

• Hoarseness is most frequent presenting complaint.

• CIS may be associated with invasive carcinoma:

  • Invasive carcinoma may occur in association with CIS or may be separate from CIS.

  • Clinically, evaluation is advised to exclude the possible presence of invasive carcinoma.

• Risk factors include:

  • Tobacco smoking (most common) and excess alcohol use:

    • –

      Alcohol potentiates the effect of tobacco smoking.

    • –

      Risk of developing dysplastic lesions increases with duration of smoking and/or alcohol use

  • Role of human papillomavirus in development of carcinoma in situ of the head and neck (other than oropharynx) not proven

Pathology

Progression to Invasive Carcinoma

• Wide variation in the literature relative to the incidence of laryngeal CIS progressing to invasive carcinoma:

  • Discrepant statistics ranging from approximately 3% to as high as 90% reflect inconsistencies in the diagnosis of CIS, which can be a notoriously subjective diagnosis.

  • Collated incidence of laryngeal CIS progressing to invasive carcinoma is 23% to 27%.

  • Latent period of 3 to 5 years from diagnosis of CIS to invasive carcinoma

Treatment and Prognosis

• No standard treatment; treatment may include:

  • Vocal cord stripping

  • Laser surgery

  • Cordectomy

  • Radiation

• Diagnosis of carcinoma in situ should prompt ablative therapy followed by surveillance for recurrence or progression:

  • Surgical excision is preferred treatment.

  • Alternative therapies such as radiation may be employed in selected patients when surgical therapy is not the best option.

• Management offers a high cure rate (approximately 75%):

  • Vigilant follow-up including periodic laryngoscopic examinations should be maintained.

• Risk factor modification remains important not only as a primary prevention strategy but to reduce risk of progression to invasive carcinoma.

• Treatment failures result from:

  • Extensive and/or multifocal disease

  • Associated undetected invasive squamous carcinoma

  • Extension of CIS to subjacent seromucous glands harboring residual disease following the mucosal stripping:

    • –

      Particularly true for CIS of the anterior commissure region, where seromucous glands may be located distant from the opening of their ducts and may lie outside area that is stripped

    • –

      For CIS of anterior commissure additional therapy including laser ablation or irradiation may be indicated.

Clinical

• Clinical manifestations are similar to those of carcinoma in situ.

• In the larynx, full cord mobility is present:

  • Any dysfunction in vocal cord mobility (fixation) by definition means muscle invasion, which excludes a diagnosis of microinvasive cancer.

• Biologically malignant lesion capable of metastasizing either via lymphatic or vascular channels

Pathology

Differential Diagnosis

• Pseudoepitheliomatous hyperplasia

• Superficial extending carcinoma (see Fig. 16-27 ):

  • Early invasive carcinoma that does not extend beyond lamina propria

  • In contrast to microinvasive carcinoma, which is predominantly an in situ carcinoma with definite but limited invasion into the lamina propria, superficial extending carcinoma shows extensive invasion into (but not beyond) the lamina propria.

  • By definition there is no invasion into muscle or cartilage.

  • Associated carcinoma in situ is often present.

  • May be multifocal

  • Establishing this diagnosis may be problematic in limited biopsy sampling and may require surgical excision with thorough histologic evaluation.

  • Limited reports to date and the long-term prognosis remains uncertain

  • Presence of nodal metastasis in the setting of superficial extending carcinoma may exclude this entity as an “early” carcinoma.