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Anterior commissure carcinoma: I-histopathologic study
Anterior Commissure Carcinoma: I-Histopathologic Study Mohamed Rifai, MD,* and Hany Khattab, MD† Objectives:To study the behavior of anterior commissure carcinoma regarding its tendency for cartilage invasion. Methods: Histopathological examination of the region of the anterior commissure (AC) was done with whole organ section in 30 randomly selected specimens. Serial sections were prepared and examined histopathologically for evidence of microscopic cartilage invasion in the region of the AC. Results: Microscopic involvement of the thyroid cartilage was detected in the 30 sections studied. Conclusion: Whether recurrence was de novo or initiated by residual malignant cells, it is mandatory to excise the anterior portion of the thyroid cartilage with the tumor-bearing mucosa. (Am J Otolaryngol 2000;21:294-297. Copyright r 2000 by W.B. Saunders Company)
Approximately 20% of all glottic tumors involve the anterior commissure (AC), with only 1% of these lesions being purely anterior commissure tumor. The AC is anatomically different from the rest of the larynx. Tumors of the AC may not impair vocal mobility because of the lack of invasion of the vocalis muscle. However, because only 2 to 3 mm separate the AC mucosa from the thyroid cartilage, a small tumor on the surface actually may invade the cartilage, thus changing the staging of the tumor. These factors greatly contribute to the controversy in the management of these tumors.1 Laryngeal carcinoma often breaks through in the anterior midline.2 There are 3 anatomical reasons for this. First, if a tumor occupies the anterior commissure, it is closer to the cartilagenous framework than anywhere else on the cords; elsewhere, muscles and perichondrium intervene. Next, in the midline, only a fibrous cord (represents the confluence of the vocal ligament, the thyroepiglottic ligament, the conus elasticus, and the internal perichondrium of the thyroid ala) separates the mucosa From the Otorhinolarygology* and Pathology† Departments, Kasr El-Aini School of Medicine, Cairo University, Cairo, Egypt. Address reprint requests to Mohamed Rifai, MD, 8 Hoda Sharawi St, Bab El Louk, 11111, Cairo, Egypt. Copyright r 2000 by W.B. Saunders Company 0196-0709/00/2105-0002$10.00/0 doi:10.1053/ajot.2000.16159 294
from the cartilage. This was named the anterior commissure tendon (ACC).2 At the insertion of the tendon, the thyroid cartilage has no inner perichondrium, which might resist tumor spread. Lastly, if a tumor spreads subglotically, it can easily penetrate the cricothyroid membrane, which is one of the weak points in the laryngeal framework.3 On the other hand, there is an oncological demarcation between the supraglottic and glottic region at a limited portion of the AC that which has been termed the ‘‘X-space.’’ The AC constitutes a preferential course for the downward spread of the supraglottic cancer mainly owing to its anatomical structure where vascular and glandular tissues abound. In the Xspace, these structures stop abruptly and are replaced by dense fibrous connective tissue. Consequently, at the level of the X-space, supraglottic cancer behaves in a distinctive way; it tends, as it spreads downward, to develop more in width than in depth. At least in an early stage, the fibrous structures of the X-space act as a barrier, and when the neoplasia does start to grow into this segment, they lead it to spread mainly along the surface.4 It is only in those unusual neoplasms that extend upward at the AC to involve the base of the epiglottis, or downward from the base of the epiglottis to the true cord, that invasion and destruction of the adjacent anterior laryngeal framework has been observed in serial
American Journal of Otolaryngology, Vol 21, No 5 (September-October), 2000: pp 294-297
ANTERIOR COMMISSURE CARCINOMA
295
sections. Of 13 nonirradiated lesions that crossed the AC in a vertical direction and were examined by whole-organ section, 10 showed invasion and destruction.4 The AC region is suggested to provide a limiting structure for lateral supraglottic lesions but is a potential pathway for spread of large glottic and midline supraglottic lesions.5 Extension to the AC diminishes control by radiotherapy as well.6 MATERIAL AND METHODS Patients Thirty laryngectomy specimens with squamous cell carcinoma of the anterior commissure were chosen for whole-organ section study. All patients were men and their ages ranged between 32 and 64 years. They all had preoperative panendoscopies to assess the extent of the tumor. Staging was established according to the 1988 American Joint Committee on Cancer classification.7 There were 24 salvage laryngectomy specimens of which 19 patients had recurrence after deep x-ray therapy (DXT) (9T1, 7T2, and 3T3), whereas 5 patients were subjected to laser excision (4T2 and 1T3). Six patients (4 T2 and 2 T3) had laryngectomy without prior therapy.
Fig 1. Histologic section showing keratinizing squamous cell carcinoma with expanding border invading the cartilage. No intervening tissue could be identified between the tumor and the cartilage (H&E; original magnification ⴛ200).
identified. In addition, no sharp demarcation could be delineated between the tumor and the underlying cartilage macroscopically. 2. Cartilage invasion and microscopic penetration at the thyroid angle by tumor cells (Fig 2). This was clearly identified in 18 of the studied specimens (4T1, 8T2, and 6T3). DISCUSSION
Histopathological Study Each excised larynx was fixed in 10% buffered formalin solution for at least 48 hours. It was then opened by a vertical cut along the midline of the posterior surface, then sliced at the region of the AC transversely or sagitally in slices of 4-mm thickness. Selected tissue sections for microscopy were decalcified, processed, and embedded in paraffin wax, cut into 5-micron thick histologic sections and stained with hematoxylin and eosin stain. Cancer invasion was looked for in the region of the angle of the thyroid cartilage.
Insertion of the AC tendon directly into the thyroid cartilage, attributable to absence internal perichondrium, may account for the frequency with which tumors are found invading cartilage at this point.4,5,8 Consequently, ACC is frequently underestimated.
RESULTS Cartilage involvement was considered positive when no intervening tissue could be detected between the tumor cells and the cartilage. All 30 sections studied showed evidence of cartilage involvement in the region of the AC as follows (Figs 1-3): 1. Cartilage invasion without penetration. Direct contact of the tumor and cartilage (Figs 1 and 3). This was noted in 12 specimen (5T1, 7T2) without evident microscopic invasion of the cartilage. No intervening mucosa could be
Fig 2. Histologic section showing nonkeratinizing squamous cell carcinoma with infiltrating border and satellites of malignant cells invading the cartilage (H&E; original magnification ⴛ200).
296
Fig 3. T1 glottic cancer seen in transverse section through the AC tendon. Note absence of fibroelastic barrier with the tumor border expanding into the cartilage (H&E; original magnification ⴛ200).
Clinically staged T3 and T4 laryngeal cancers underwent wide-field total laryngectomy and were processed as whole-organ serial sections in the coronal plane to measure the incidence of clinically underestimated laryngeal cancer. Clinical underestimation had been made in approximately 50% of the T3 laryngeal cancer cases. The extent of cartilage involvement in the underestimated group was characterized by microinvasion without penetration.9 One of the most important indicators of thyroid cartilage penetration is extensive involvement of the anterior commissure (67%). Clinical underestimation of T4 laryngeal cancers was high because thyroid cartilage involvement was not accurately diagnosed.9 The present study confirmed cartilage invasion in all studied cases of primary and recurrent AC carcinoma. Accordingly, all studied cases were T4 and were thus understaged. In the present study, 19 cases of AC carcinoma showed recurrence and cartilage invasion after DXT. Similar observations were encoun-
RIFAI AND KHATTAB
tered in 5 patients after laser excision. Identification of malignant invasion of the AC in the 6 nonrecurrent cases may arouse the suspicion of this as being the trigger for recurrence in those 24 recurrent cases. The thyroid cartilage starts to ossify by the age of 30 in an irregular manner, thereby making it difficult to properly assess cartilage invasion by computed tomography or magnetic resonance imaging. Actually, pretreatment assessment of the extent of the tumor is not entirely satisfactory by any modality. Cartilage invasion should always be anticipated in ACC, which should be therefore staged as T4. ACC therefore deserves more radical surgery where the central portion of the thyroid cartilage should be excised.10,11 Laser excision and DXT should be reconsidered as a modality of treatment for lesions at this site.3,6,10,11 Serial section study of the AC is mandatory because cartilage invasion may be absent at one level while present in others. In the presence of poorly oxygenated microscopic cartilage invasion, it is almost unlikely for DXT to eradicate ACC with potential risk of perichondritis. It seems also difficult to trace tumor cells within the cartilage with almost certainty of microscopic malignant cells left behind. Whether recurrence was de novo or initiated by residual malignant cells, treatment is safely achieved by complete extirpation of the central portion of the thyroid angle to include the AC. CONCLUSION Anterior commissure carcinoma is frequently understaged. Whole-organ section study of 30 excised larynges of ACC confirmed cartilage invasion of the AC in all studied specimens. This may account for recurrence after DXT and laser therapy, which are better avoided in cases where carcinoma is reaching the AC. Surgical excision of the central portion of the thyroid cartilage seems to be the method of choice to treat ACC. REFERENCES 1. Krespi YP, Meltzer CJ: Laser surgery for vocal cord carcinoma involving the anterior commissure. Ann Otol Rhinol Laryngol 98:105-109, 1989 2. Broyles EN: The anterior commissure tendon. Ann Otol Rhinol Laryngol 52:342-345, 1943 3. Olofsson J, Williams GT, Rider WD, et al: Anterior
ANTERIOR COMMISSURE CARCINOMA
commissure carcinoma: Primary treatment with radiotherapy in 57 patients. Arch Otolaryngol 95:230-239, 1972 4. Bagatelli F, Bignardi L: Behaviour of cancer at the anterior commissure of the larynx. Laryngoscope 93:353356, 1983 5. Kirchner JA, Carter D: Intralaryngeal barriers to the spread of cancer. Acta Otolaryngol (Stockh) 103:503-513, 1987 6. Zohar Y, Rahima M, Shivili Y, et al: The controversial treatment of anterior commissure carcinoma of the larynx. Laryngoscope 102:69-72, 1992 7. Beahrs OH, Henson DE, Hutter RVP, et al (eds):
297
American Joint Committee on Cancer (ed 3). Philadelphia, PA, Lippincott, 1988, pp 9-44 8. Kirchner JA: Anterior commissure cancer. Can J Otolaryngol 4:671, 1975 9. Nakayama M, Brandenburg JH: Clinical understimulation of laryngeal cancer. Predictive indicators. Arch Otolaryngol Head Neck Surg 119:950-957, 1993 10. Bailey BJ (ed): Glottic carcinoma, in Surgery of the Larynx. Saunders, Philadelphia, PA, 1985, p 267 11. Davis RK, Jako GJ, Hyams VJ, et al: The anatomical limitations of CO2 laser cordectomy. Laryngoscope 92: 980, 1982
Approximately 20% of all glottic tumors involve the anterior commissure (AC), with only 1% of these lesions being purely anterior commissure tumor. The AC is anatomically different from the rest of the larynx. Tumors of the AC may not impair vocal mobility because of the lack of invasion of the vocalis muscle. However, because only 2 to 3 mm separate the AC mucosa from the thyroid cartilage, a small tumor on the surface actually may invade the cartilage, thus changing the staging of the tumor. These factors greatly contribute to the controversy in the management of these tumors.1 Laryngeal carcinoma often breaks through in the anterior midline.2 There are 3 anatomical reasons for this. First, if a tumor occupies the anterior commissure, it is closer to the cartilagenous framework than anywhere else on the cords; elsewhere, muscles and perichondrium intervene. Next, in the midline, only a fibrous cord (represents the confluence of the vocal ligament, the thyroepiglottic ligament, the conus elasticus, and the internal perichondrium of the thyroid ala) separates the mucosa From the Otorhinolarygology* and Pathology† Departments, Kasr El-Aini School of Medicine, Cairo University, Cairo, Egypt. Address reprint requests to Mohamed Rifai, MD, 8 Hoda Sharawi St, Bab El Louk, 11111, Cairo, Egypt. Copyright r 2000 by W.B. Saunders Company 0196-0709/00/2105-0002$10.00/0 doi:10.1053/ajot.2000.16159 294
from the cartilage. This was named the anterior commissure tendon (ACC).2 At the insertion of the tendon, the thyroid cartilage has no inner perichondrium, which might resist tumor spread. Lastly, if a tumor spreads subglotically, it can easily penetrate the cricothyroid membrane, which is one of the weak points in the laryngeal framework.3 On the other hand, there is an oncological demarcation between the supraglottic and glottic region at a limited portion of the AC that which has been termed the ‘‘X-space.’’ The AC constitutes a preferential course for the downward spread of the supraglottic cancer mainly owing to its anatomical structure where vascular and glandular tissues abound. In the Xspace, these structures stop abruptly and are replaced by dense fibrous connective tissue. Consequently, at the level of the X-space, supraglottic cancer behaves in a distinctive way; it tends, as it spreads downward, to develop more in width than in depth. At least in an early stage, the fibrous structures of the X-space act as a barrier, and when the neoplasia does start to grow into this segment, they lead it to spread mainly along the surface.4 It is only in those unusual neoplasms that extend upward at the AC to involve the base of the epiglottis, or downward from the base of the epiglottis to the true cord, that invasion and destruction of the adjacent anterior laryngeal framework has been observed in serial
American Journal of Otolaryngology, Vol 21, No 5 (September-October), 2000: pp 294-297
ANTERIOR COMMISSURE CARCINOMA
295
sections. Of 13 nonirradiated lesions that crossed the AC in a vertical direction and were examined by whole-organ section, 10 showed invasion and destruction.4 The AC region is suggested to provide a limiting structure for lateral supraglottic lesions but is a potential pathway for spread of large glottic and midline supraglottic lesions.5 Extension to the AC diminishes control by radiotherapy as well.6 MATERIAL AND METHODS Patients Thirty laryngectomy specimens with squamous cell carcinoma of the anterior commissure were chosen for whole-organ section study. All patients were men and their ages ranged between 32 and 64 years. They all had preoperative panendoscopies to assess the extent of the tumor. Staging was established according to the 1988 American Joint Committee on Cancer classification.7 There were 24 salvage laryngectomy specimens of which 19 patients had recurrence after deep x-ray therapy (DXT) (9T1, 7T2, and 3T3), whereas 5 patients were subjected to laser excision (4T2 and 1T3). Six patients (4 T2 and 2 T3) had laryngectomy without prior therapy.
Fig 1. Histologic section showing keratinizing squamous cell carcinoma with expanding border invading the cartilage. No intervening tissue could be identified between the tumor and the cartilage (H&E; original magnification ⴛ200).
identified. In addition, no sharp demarcation could be delineated between the tumor and the underlying cartilage macroscopically. 2. Cartilage invasion and microscopic penetration at the thyroid angle by tumor cells (Fig 2). This was clearly identified in 18 of the studied specimens (4T1, 8T2, and 6T3). DISCUSSION
Histopathological Study Each excised larynx was fixed in 10% buffered formalin solution for at least 48 hours. It was then opened by a vertical cut along the midline of the posterior surface, then sliced at the region of the AC transversely or sagitally in slices of 4-mm thickness. Selected tissue sections for microscopy were decalcified, processed, and embedded in paraffin wax, cut into 5-micron thick histologic sections and stained with hematoxylin and eosin stain. Cancer invasion was looked for in the region of the angle of the thyroid cartilage.
Insertion of the AC tendon directly into the thyroid cartilage, attributable to absence internal perichondrium, may account for the frequency with which tumors are found invading cartilage at this point.4,5,8 Consequently, ACC is frequently underestimated.
RESULTS Cartilage involvement was considered positive when no intervening tissue could be detected between the tumor cells and the cartilage. All 30 sections studied showed evidence of cartilage involvement in the region of the AC as follows (Figs 1-3): 1. Cartilage invasion without penetration. Direct contact of the tumor and cartilage (Figs 1 and 3). This was noted in 12 specimen (5T1, 7T2) without evident microscopic invasion of the cartilage. No intervening mucosa could be
Fig 2. Histologic section showing nonkeratinizing squamous cell carcinoma with infiltrating border and satellites of malignant cells invading the cartilage (H&E; original magnification ⴛ200).
296
Fig 3. T1 glottic cancer seen in transverse section through the AC tendon. Note absence of fibroelastic barrier with the tumor border expanding into the cartilage (H&E; original magnification ⴛ200).
Clinically staged T3 and T4 laryngeal cancers underwent wide-field total laryngectomy and were processed as whole-organ serial sections in the coronal plane to measure the incidence of clinically underestimated laryngeal cancer. Clinical underestimation had been made in approximately 50% of the T3 laryngeal cancer cases. The extent of cartilage involvement in the underestimated group was characterized by microinvasion without penetration.9 One of the most important indicators of thyroid cartilage penetration is extensive involvement of the anterior commissure (67%). Clinical underestimation of T4 laryngeal cancers was high because thyroid cartilage involvement was not accurately diagnosed.9 The present study confirmed cartilage invasion in all studied cases of primary and recurrent AC carcinoma. Accordingly, all studied cases were T4 and were thus understaged. In the present study, 19 cases of AC carcinoma showed recurrence and cartilage invasion after DXT. Similar observations were encoun-
RIFAI AND KHATTAB
tered in 5 patients after laser excision. Identification of malignant invasion of the AC in the 6 nonrecurrent cases may arouse the suspicion of this as being the trigger for recurrence in those 24 recurrent cases. The thyroid cartilage starts to ossify by the age of 30 in an irregular manner, thereby making it difficult to properly assess cartilage invasion by computed tomography or magnetic resonance imaging. Actually, pretreatment assessment of the extent of the tumor is not entirely satisfactory by any modality. Cartilage invasion should always be anticipated in ACC, which should be therefore staged as T4. ACC therefore deserves more radical surgery where the central portion of the thyroid cartilage should be excised.10,11 Laser excision and DXT should be reconsidered as a modality of treatment for lesions at this site.3,6,10,11 Serial section study of the AC is mandatory because cartilage invasion may be absent at one level while present in others. In the presence of poorly oxygenated microscopic cartilage invasion, it is almost unlikely for DXT to eradicate ACC with potential risk of perichondritis. It seems also difficult to trace tumor cells within the cartilage with almost certainty of microscopic malignant cells left behind. Whether recurrence was de novo or initiated by residual malignant cells, treatment is safely achieved by complete extirpation of the central portion of the thyroid angle to include the AC. CONCLUSION Anterior commissure carcinoma is frequently understaged. Whole-organ section study of 30 excised larynges of ACC confirmed cartilage invasion of the AC in all studied specimens. This may account for recurrence after DXT and laser therapy, which are better avoided in cases where carcinoma is reaching the AC. Surgical excision of the central portion of the thyroid cartilage seems to be the method of choice to treat ACC. REFERENCES 1. Krespi YP, Meltzer CJ: Laser surgery for vocal cord carcinoma involving the anterior commissure. Ann Otol Rhinol Laryngol 98:105-109, 1989 2. Broyles EN: The anterior commissure tendon. Ann Otol Rhinol Laryngol 52:342-345, 1943 3. Olofsson J, Williams GT, Rider WD, et al: Anterior
ANTERIOR COMMISSURE CARCINOMA
commissure carcinoma: Primary treatment with radiotherapy in 57 patients. Arch Otolaryngol 95:230-239, 1972 4. Bagatelli F, Bignardi L: Behaviour of cancer at the anterior commissure of the larynx. Laryngoscope 93:353356, 1983 5. Kirchner JA, Carter D: Intralaryngeal barriers to the spread of cancer. Acta Otolaryngol (Stockh) 103:503-513, 1987 6. Zohar Y, Rahima M, Shivili Y, et al: The controversial treatment of anterior commissure carcinoma of the larynx. Laryngoscope 102:69-72, 1992 7. Beahrs OH, Henson DE, Hutter RVP, et al (eds):
297
American Joint Committee on Cancer (ed 3). Philadelphia, PA, Lippincott, 1988, pp 9-44 8. Kirchner JA: Anterior commissure cancer. Can J Otolaryngol 4:671, 1975 9. Nakayama M, Brandenburg JH: Clinical understimulation of laryngeal cancer. Predictive indicators. Arch Otolaryngol Head Neck Surg 119:950-957, 1993 10. Bailey BJ (ed): Glottic carcinoma, in Surgery of the Larynx. Saunders, Philadelphia, PA, 1985, p 267 11. Davis RK, Jako GJ, Hyams VJ, et al: The anatomical limitations of CO2 laser cordectomy. Laryngoscope 92: 980, 1982