Upper Aerodigestive Tract (Including Salivary Glands) Protocol applies to all invasive carcinomas of the upper aerodigestive tract including the oral cavity (including lip and tongue), pharynx


Primary Tumor (T): Salivary Glands



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Primary Tumor (T): Salivary Glands


TX Primary tumor cannot be assessed

T0 No evidence of primary tumor

T1 Tumor 2 cm or less in greatest dimension without extraparenchymal extension#

T2 Tumor more than 2 cm but not more than 4 cm in greatest dimension without extraparenchymal extension#

T3 Tumor more than 4 cm and/or tumor with extraparenchymal extension

T4a Tumor invades skin, mandible, ear canal, or facial nerve

T4b Tumor invades base of skull, pterygoid plates, or encases carotid artery
# Extraparenchymal extension is clinical or macroscopic evidence of invasion of soft tissues or nerve except those listed under T4a and 4b. Microscopic evidence alone does not constitute extraparenchymal extension for classification purposes.

Regional Lymph Nodes (N): Salivary Glands


NX Regional lymph nodes cannot be assessed

N0 No regional lymph node metastasis

N1 Metastasis in a single ipsilateral lymph node, 3 cm or less in greatest dimension

N2 Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension; or in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension; or in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension

N2a Metastasis in a single ipsilateral lymph node, more than 3 cm but not more than 6 cm in greatest dimension

N2b Metastasis in multiple ipsilateral lymph nodes, none more than 6 cm in greatest dimension

N2c Metastasis in bilateral or contralateral lymph nodes, none more than 6 cm in greatest dimension

N3 Metastasis in a lymph node more than 6 cm in greatest dimension



Distant Metastasis (M): Salivary Glands


MX Distant metastasis cannot be assessed

M0 No distant metastasis

M1 Distant metastasis

Stage Groupings: Salivary Glands


Stage I T1 N0 M0

Stage II T2 N0 M0

Stage III T3 N0 M0

T1,T2,T3 N1 M0

Stage IVA T1,T2,T3 N2 M0

T4a N0,N1,N2 M0

Stage IVB T4b Any N M0

Any T N3 M0

Stage IVC Any T Any N M1

TNM Descriptors


For identification of special cases of TNM or pTNM classifications, the “m” suffix and “y,” “r,” and “a” prefixes are used. Although they do not affect the stage grouping, they indicate cases needing separate analysis.
The “m” suffix indicates the presence of multiple primary tumors in a single site and is recorded in parentheses: pT(m)NM.
The “y” prefix indicates those cases in which classification is performed during or following initial multimodality therapy (ie, neoadjuvant chemotherapy, radiation therapy, or both chemotherapy and radiation therapy). The cTNM or pTNM category is identified by a “y” prefix. The ycTNM or ypTNM categorizes the extent of tumor actually present at the time of that examination. The “y” categorization is not an estimate of tumor prior to multimodality therapy (ie, before initiation of neoadjuvant therapy).
The “r” prefix indicates a recurrent tumor when staged after a documented disease-free interval, and is identified by the “r” prefix: rTNM.
The “a” prefix designates the stage determined at autopsy: aTNM.

Additional Descriptors

Residual Tumor (R)


Tumor remaining in a patient after therapy with curative intent (eg, surgical resection for cure) is categorized by a system known as R classification, shown below.
RX Presence of residual tumor cannot be assessed

R0 No residual tumor

R1 Microscopic residual tumor

R2 Macroscopic residual tumor


For the surgeon, the R classification may be useful to indicate the known or assumed status of the completeness of a surgical excision. For the pathologist, the R classification is relevant to the status of the margins of a surgical resection specimen. That is, tumor involving the resection margin on pathologic examination may be assumed to correspond to residual tumor in the patient. and may be classified as macroscopic or microscopic according to the findings at the specimen margin(s).

Vessel Invasion


By AJCC/UICC convention, vessel invasion (lymphatic or venous) does not affect the T category indicating local extent of tumor unless specifically included in the definition of a T category. In all other cases, lymphatic and venous invasion by tumor are coded separately as follows.

Lymphatic Vessel Invasion (L)


LX Lymphatic vessel invasion cannot be assessed

L0 No lymphatic vessel invasion

L1 Lymphatic vessel invasion

Venous Invasion (V)


VX Venous invasion cannot be assessed

V0 No venous invasion

V1 Microscopic venous invasion

V2 Macroscopic venous invasion



Regional Lymph Nodes (pN0): Isolated Tumor Cells


Isolated tumor cells (ITCs) are single cells or small clusters of cells not more than 0.2 mm in greatest dimension. Lymph nodes or distant sites with ITCs found by either histologic examination, immunohistochemistry, or nonmorphologic techniques (eg, flow cytometry, DNA analysis, polymerase chain reaction [PCR] amplification of a specific tumor marker) should be classified as N0 or M0, respectively. Specific denotation of the assigned N category is suggested as follows for cases in which ITCs are the only evidence of possible metastatic disease.3,4
pN0 No regional lymph node metastasis histologically, no examination for isolated tumor cells (ITCs)

pN0(i-) No regional lymph node metastasis histologically, negative morphologic (any morphologic technique, including hematoxylin-eosin and immunohistochemistry) findings for ITCs

pN0(i+) No regional lymph node metastasis histologically, positive morphologic (any morphologic technique, including hematoxylin-eosin and immunohistochemistry) findings for ITCs

pN0(mol-) No regional lymph node metastasis histologically, negative nonmorphologic (molecular) findings for ITCs

pN0(mol+) No regional lymph node metastasis histologically, positive nonmorphologic (molecular) findings for ITCs

F. Lymph Nodes


The status of cervical lymph nodes is the single most important prognostic factor in aerodigestive cancer. For purposes of pathologic evaluation, lymph nodes are organized by levels as shown in Figure 2.5,6


Figure 2. The lymph node groups included in the node dissection specimens should be designated as shown in the figure and identified with the assistance of the surgeon in charge, whenever possible.
P: Parotid-Preauricular.
R: Retroauricular.
S: Suboccipital.

From: Cummings CW, ed. Otolaryngology Head and Neck Surgery. 2nd ed. St. Louis: Mosby, Inc; 1992:1652. Reprinted with permission.


In order for pathologists to properly identify these nodes, they must be familiar with the terminology of the regional lymph node groups and with the relationships of those groups to the regional anatomy. Which lymph node groups surgeons submit for histopathologic evaluation depends on the type of neck dissection they perform. Therefore, surgeons must supply information on the types of neck dissections that they perform and on the details of the local anatomy in the specimens they submit for examination, or in other manners, orient those specimens for pathologists.
If it is not possible to assess the levels of lymph nodes (for instance, when the anatomic landmarks in the excised specimens are not specified), then the lymph node levels may be estimated as follows: level II, upper third of internal jugular (IJ) vein or neck specimen; level III, middle third of IJ vein or neck specimen; level IV, lower third of IJ vein or neck specimen, all anterior to the sternocleidomastoid muscle.

Level I. Submental Group


Lymph nodes within the triangular boundary of the anterior belly of the digastric muscles and the hyoid bone.

Submandibular Group


Lymph nodes within the boundaries of the anterior and posterior bellies of the digastric muscle and the body of the mandible. The submandibular gland is included in the specimen when the lymph nodes within this triangle are removed.

Level II. Upper Jugular Group


Lymph nodes located around the upper third of the internal jugular vein and adjacent spinal accessory nerve extending from the level of the carotid bifurcation (surgical landmark) or hyoid bone (clinical landmark) to the skull base. The posterior boundary is the posterior border of the sternocleidomastoid muscle, and the anterior boundary is the lateral border of the sternohyoid muscle.

Level III. Middle Jugular Group


Lymph nodes located around the middle third of the internal jugular vein extending from the carotid bifurcation superiorly to the omohyoid muscle (surgical landmark), or cricothyroid notch (clinical landmark) inferiorly. The posterior boundary is the posterior border of the sternocleidomastoid muscle, and the anterior boundary is the lateral border of the sternohyoid muscle.

Level IV. Lower Jugular Group


Lymph nodes located around the lower third of the internal jugular vein extending from the omohyoid muscle superiorly to the clavicle inferiorly. The posterior boundary is the posterior border of the sternocleidomastoid muscle, and the anterior boundary is the lateral border of the sternohyoid muscle.

Level V. Posterior Triangle Group


This group comprises predominantly the lymph nodes located along the lower half of the spinal accessory nerve and the transverse cervical artery. The supraclavicular nodes are also included in this group. The posterior boundary of the posterior triangle is the anterior border of the trapezius muscle, the anterior boundary of the posterior triangle is the posterior border of the sternocleidomastoid muscle, and the inferior boundary of the posterior triangle is the clavicle.
Lymph node groups removed from areas not included in the above levels, eg, scalene, suboccipital and retropharyngeal, should be identified and reported from all levels separately. When staging lymph node involvement by metastases from nasopharyngeal carcinoma, the supraclavicular fossa refers to a triangular region, the base of which is the superior margin of the clavicle between its sternal and lateral ends, and the apex of which is the point where the neck meets the shoulder. This includes caudal portions of Levels IV and V (see above). All cancers metastatic to the posterior nodes in the supraclavicular fossa are designated as N3b.

G. Lymph Node Number


Histological examination of a selective neck dissection specimen will ordinarily include 6 or more lymph nodes. Histological examination of a radical or modified radical neck dissection specimen will ordinarily include 10 or more lymph nodes in the untreated neck.

H. Measurement of Tumor Metastasis


The cross-sectional diameter of the largest metastasis in a lymph node containing metastatic tumor is measured in the gross specimen at the time of macroscopic examination or if necessary, on the histologic slide at the time of microscopic examination. The prognostic impact of regional lymph node metastases from nasopharyngeal cancer, particularly undifferentiated nasopharyngeal carcinoma (lymphoepithelioma), differs from and is not necessarily comparable to the prognoses of other head and neck mucosal carcinomas. Therefore, a different N classification scheme is used for nasopharyngeal carcinoma.

References


1. Greene FL, Page DL, Fleming ID, et al, eds. AJCC Cancer Staging Manual. 6th ed. New York: Springer; 2002.

2. Sobin LH, Wittekind C. UICC TNM Classification of Malignant Tumours. 6th ed. New York: Wiley-Liss; 2002.

3. Wittekind C, Greene FL, Henson DE, Hutter RVP, Sobin LH, eds. TNM Supplement. A Commentary on Uniform Use. 3rd ed. New York: Wiley-Liss; 2003.
4. Singletary SE, Greene FL, Sobin LH. Classification of isolated tumor cells: clarification of the 6th edition of the American Joint Committee on Cancer Staging Manual. Cancer. 2003;90(12):2740-2741.

5. Medina, JE. Neck dissection. In: Cummings CW, ed. Otolaryngology Head and Neck Surgery. 2nd ed. St. Louis, Mo: The CV Mosby Co; 1992:1649-1672.

6. Robbins T, Medina JE, Wolfe GT, Levine PA, Sessions RB, Pruet CW. Standardizing neck dissection terminology: official report of the academy’s committee for head and neck surgery and oncology. Arch Otolaryngol Head Neck Surg. 1991;117:601-605.

Bibliography

General


Batsakis JE. Tumors of the Head and Neck. 2nd ed. Baltimore, Md: William and Wilkins; 1979.

Enroth CM. Salivary gland tumors in the parotid gland, submandibular gland and the palate region. Cancer. 1991;27:1415-1418.

Mendenhall WM, Parsons JT, Stringer SP, Cassisi NJ, Million RR. The role of radiation therapy in laryngeal cancer. CA Cancer J Clin. 1990;40:150-165.

Robbins KT, Medina JE, Wolfe GT, Levine PA, Sessions RB, Pruet CW. Standardizing neck dissection terminology. Arch Otolaryngol Head Neck Surg. 1991;117:601-605.

Shah JP. Patterns of cervical lymph node metastasis from squamous carcinoma of the upper aerodigestive tract. Am J Surg. 1990;160:405-409.

Shah JP, Ihde JK. Salivary gland tumors. Curr Probl Surg. 1990;27:775-883.

Shah JP, Medina J, Shaha AR, Schantz SP, Marti JR. Cervical lymph node metastasis. Curr Probl Surg. 1993;30:273-344.

Spiro RH. Salivary neoplasms: overview of a 35-year experience with 2,807 patients. Head Neck Surg. 1986;8:177-184.

Vokes EE, Weichselbaum RR. Chemoradio-therapy for head and neck cancer. In: PPO Updates. Vol. 7, No. 6. Philadelphia, Pa: JB Lippincott Co; 1993.

Vokes EE, Weichselbaum RR, Lippman SM, Hong WK. Head and neck cancer. N Engl J Med. 1993;328:184-194.

Wolf GT, Maruch RV, Baker SR. Predictive factors for tumor response to preoperative chemotherapy in patients with head and neck squamous carcinoma. Cancer. 1984;54:2869-2877.

Histologic Grade


Crissman JD, Sakr WA. Squamous neoplasia of the upper areodigestive tract. Intraepithelial and invasive squamous cell carcinoma. In: Pilch BZ, ed. Head and Neck Surgical Pathology. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001:42-43.

Ellis GL, Auclair PL. Tumors of the salivary glands. In: Atlas of Tumor Pathology. 3rd Series, Fascicle 17. Washington, DC: Armed forces Institute of Pathology; 1996.

Frierson HF, Cooper PH. Prognostic factors in squamous cell carcinoma of the lower lip Hum Pathol. 1986;17:346-354.

McGavran MH, Bauer WC, Ogura JH. The incidence of cervical lymph node metastases from epidermoid carcinoma of the larynx and their relationship to certain characteristics of the primary tumor: a study based on the clinical and pathological findings for 96 patients treated by primary en bloc laryngectomy and radical neck dissection. Cancer. 1961;14:55-65.

Mendelson BC, Woods JE, Beahrs OH. Neck dissection in the treatment of carcinoma of the anterior two thirds of the tongue. Surg Gynaecol Obstet. 1976;143:75-80.

Mills SE, Gaffey MJ, Frierson HF, Jr. Tumors of the upper aerodigestive tract and ear. In: Atlas of Tumor Pathology. 3rd Series. Fascicle 26. Washington, DC: Armed forces Institute of Pathology; 2000:16.

Umeda M, Yokoo S, Take Y, Omori A. Lymph node metastasis in squamous cell carcinoma of the oral cavity: correlation between histologic features and the prevalence of metastasis. Head Neck Surg. 1992;14:263-272.

Willen R, Nathanson A, Moberger C, Anneroth G. Squamous cell carcinoma of the gingiva: histological classification and grading of malignancy. Acta Otolaryngol. 1975;79:146-154.



Vascular Invasion


Close LG, Burns DK, Reisch J, Schaefer DS. Microvascular invasion in cancer of the oral cavity and oropharynx. Arch Otolaryngol Head Neck Surg. 1987;113:1191-1195.

Crissman JD, Liu WY, Gluckman JL, Cummings G. Prognostic value of histopathologic parameters in squamous cell carcinoma of the oropharynx. Cancer. 1984;54:2995-3001.

Frierson HF, Cooper PH. Prognostic factors in squamous cell carcinoma of the lower lip. Hum Pathol. 1986;17:346-354.

McGavran MH, Bauer WC, Ogura JH. The incidence of cervical lymph node metastases from epidermoid carcinoma of the larynx and their relationship to certain characteristics of the primary tumor: a study based on the clinical and pathological findings for 96 patients treated by primary en bloc laryngectomy and radical neck dissection. Cancer. 1961;14:55-65.

Poleksic S, Kalwaic JH. Prognostic value of vascular invasion in squamous cell carcinoma of the head and neck. Plast Reconstr Surg. 1978;61:234-240.

Perineural Invasion


Close LG, Burns DK, Reisch J, Schaefer SD. Microvascular invasion in cancer of the oral cavity and oropharynx. Arch Otolaryngol Head Neck Surg. 1987;113:1191-1195.

Frierson HF, Cooper PH. Prognostic factors in squamous cell carcinoma of the lower lip. Hum Pathol. 1986;17:346-354.

Willen R, Nathanson A, Moberger C, Anneroth G. Squamous cell carcinoma of the gingiva: histological classification and grading of malignancy. Acta Otolaryngol. 1975;79:146-154.

Surgical Margins


Laramore GE, Scott CB, al-Sarraf M, et al. Adjuvant chemotherapy for resectable squamous cell carcinomas of the head and neck: report on Intergroup Study 0034. Int J Radiat Oncol Biol Phys. 1992;23:705-713.

Zelefsky MJ, Harrison LB, Fass DE, Armstrong JG, Shah JP, Strong EW. Postoperative radiation therapy for squamous cell carcinomas of the oral cavity and oropharynx: impact of therapy on patients with positive surgical margins. Int J Radiat Oncol Biol Phys. 1993;25:17-21.



Extranodal Extension


Carter R. The pathologist’s appraisal of neck dissections. Eur Arch Otorhino-laryngol. 1993;250:429-431.

Don DM, Anzai Y, Lufkin RB, Fu YS, Calcaterra TC. Evaluation of cervical lymph node metastases in squamous cell carcinoma of the head and neck. Laryngoscope. 1995;105:669-674.

Leemans CR, Tiwari R, Nauta JJ, van der Waal I, Snow GB. Regional lymph node involvement and its significance in the development of distant metastases in head and neck carcinoma. Cancer. 1993;71:452-456.

Johnson JT, Barnes EL, Meyers EN, et al. The extracapsular spread of tumors in cervical node metastases. Head Neck Surg. 1981;107:725-729



Levels and Size of Nodes


Lindberg R. Distribution of cervical lymph node metastases from squamous cell carcinoma of the upper respiratory and digestive tracts. Cancer. 1972;29:1446-1449.

Number of Nodes


Kalnins IK, Leonard AG, Sako K, et al. Correlation between prognosis and degree of lymph node involvement in carcinoma of the oral cavity. Am J Surg. 1977;134:450-454.

Malmelle G, Pampurik J. Luboinski B, et al. Lymph node prognostic factor in head and neck squamous carcinomas. Am J Surg. 1994;168:494-498.

O’Brien CJ, Smith JW, Soong SJ, Urist MM, Maddox WA. Neck dissection with and without radiotherapy: prognostic factors, patterns of recurrence and survival. Am J Surg. 1986;152:456-463.

Ono I, Ebihara S, Saito H, et al. Correlation between prognosis and degree of lymph node involvement in carcinoma of the head and neck. Auris nasus Larynx. 1985;12:S86-S89.

Pinsolle J, Pinsolle V, Majoufre C, et al. Prognostic value of histologic findings in neck dissections for squamous cell carcinoma. Arch Otolaryngol Head Neck Surgery. 1997;123:145-148.

Shah JP, Cendon RA, Farr HW, Strong EW: Carcinoma of the oral cavity: factors affecting treatment failure at the primary site and neck. Am J Surg. 1976;132:504-507.

Spiro RH, Alfonso AE, Farr HW, Strong EW. Cervical node metastasis from epidermoid carcinoma of the oral cavity and oropharynx. A critical assessment of current staging. Am J Surg. 1974;128:562-567.

Whitehurst JO, Droulias CA. Surgical treatment of squamous cell carcinoma of the oral tongue. Arch Otolaryngol. 1977;103:212-215.



Type of Margin


Crissman JD, Liu WY, Gluckman JL, Cummings G. Prognostic value of histopathologic parameters in squamous cell carcinoma of the oropharynx. Cancer. 1984;54:2995-3001.

Frierson HF, Cooper PH. Prognostic factors in squamous cell carcinoma of the lower lip. Hum Pathol. 1986;17:346-354.

Umeda M, Yokoo S, Take Y, Omori A. Lymph node metastasis in squamous cell carcinoma of the oral cavity: correlation between histologic features and the prevalence of metastasis. Head Neck Surg. 1992;14:263-272.

Willen R, Nathanson A, Moberger C, Anneroth G. Squamous cell carcinoma of the gingiva: histological classification and grading of malignancy. Acta Otolaryngol. 1975;79:146-154.

Yamamoto E, Miyakawa A, Kohama G. Mode of invasion and lymph node metastasis in squamous cell carcinoma of the oral cavity. Head Neck Surg. 1984;6:938-947.

Thickness of Tumor


Borges AM, Shrikhande SS, Ganesh B. Surgical pathology of squamous carcinoma of the oral cavity: its impact on management. Semin Surg Oncol. 1989;5:310-317.

Brown B, Barnes L, Mazariegos J, Taylor F, Johnson J, Wagner RL. Prognostic factors in mobile tongue and floor of mouth carcinoma. Cancer. 1989;64:1195-1202.

Frierson HF, Cooper PH. Prognostic factors in sqamous cell carcinoma of the lower lip. Hum Pathol. 1986;17:346-354.

Mohit-Tabatabai MA, Sobel HJ, Rush BF, Mashberg A. Relation of thickness of floor of mouth stage I and II cancers to regional metastasis. Am J Surg. 1986;152:351-353.

Rasgon BM, Cruz RM, Hilsinger RL, Sawicki JE. Relation of lymph node metastasis to histopathologic appearance in oral cavity and oropharyngeal carcinoma: a case series and literature review. Laryngoscope. 1989;99:1103-1110.

Spiro RH, Huvos AG, Wong GY, Spiro JD. Predictive value of tumor thickness in squamous cell carcinoma confined to the tongue and floor of the mouth. Am J Surg. 1986;152:345-350.

Tralongo V, et al Prognostic factors in oral squamous cell carcinoma. Anticancer Research. 1999;19(4c):3505-3510.

Yuen AP et al, A comparison of the prognostic significance of tumor diameter, length, width, thickness, area, volume, and clinicopathological features of oral tongue carcinoma. Am J Surg. 2000;180(2):139-143.






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