Basaloid squamous cell carcinoma of the larynx

Basaloid squamous cell carcinoma of the larynx

Basaloid squamous cell carcinoma of the larynx TZUNG-SHIAHN SHEEN, MD, YIH-LEONG CHANG, MD, JENQ-YUH KO, MD, CHEN-TU WU, MD, and SHIANN-YANN LEE, MD, ...

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Basaloid squamous cell carcinoma of the larynx TZUNG-SHIAHN SHEEN, MD, YIH-LEONG CHANG, MD, JENQ-YUH KO, MD, CHEN-TU WU, MD, and SHIANN-YANN LEE, MD,

Taipei, Taiwan

C

arcinoma of the larynx is not an uncommon disease. More than 85% of the epithelial malignancies of the larynx are squamous cell carcinoma. Other carcinomas, such as undifferentiated carcinoma, verrucous carcinoma, pleomorphic carcinoma, mucoepidermoid carcinoma, and adenocarcinoma, are occasionally encountered.1 The MEDLINE database was searched from 1966 to 1996, but only some sporadic series in the English language literature reported basaloid squamous cell carcinoma of the head and neck.2-12 In the larynx, most of these tumors were located in supraglottis, with the involvement of tongue base or pyriform sinus. The prognosis for these patients was usually poor; most died of local recurrence or distant metastasis despite aggressive treatment. This case report is of a patient with early glottic basaloid squamous cell carcinoma who was successfully treated with partial vertical laryngectomy. CASE REPORT

A 50-year-old man visited our hospital in 1983 with the chief symptom of hoarseness of 4 months’ duration. He was a heavy smoker and alcohol consumer. A tumor of the larynx was noticed under indirect laryngoscopy. The mobility of both vocal cords was normal and symmetric. Under direct laryngoscopy, this papillomatous, polypoid tumor was located at the anterior portion of his left vocal cord with the involvement of anterior commissure (Fig 1). A biopsy specimen showed nests of tumor cells with basophilic cytoplasm and uniform nuclei, with palisading arrangement at the periphery. There were also some areas of conventional squamous cell carcinoma with keratin pearl formation (Fig 2). These findings met the diagnostic criteria of a basaloid squamous cell carcinoma. He underwent partial vertical laryngectomy with epiglottis reconstruction. The margins of resection were free of tumor. The postoperative course was uneventful, and he did not undergo radiotherapy. He has been followed up regularly at

From the Departments of Otolaryngology (Drs. Sheen, Ko, and Lee) and Pathology (Drs. Chang and Wu), National Taiwan University Hospital, College of Medicine. Reprint requests: Tzung-Shiahn Sheen, MD, Department of Otolaryngology, National Taiwan University Hospital, No. 7, Chung-Shan South Rd., Taipei, Taiwan. Otolaryngol Head Neck Surg 1999;121:647-50. Copyright © 1999 by the American Academy of Otolaryngology– Head and Neck Surgery Foundation, Inc. 0194-5998/99/$8.00 + 0 23/78/87117

our hospital for 13 years with no sign of local recurrence or distant metastasis. IMMUNOHISTOCHEMISTRY Formalin-fixed, paraffin-embedded tissue sections with a thickness of 4 µm were used for immunohistochemical staining study. These tissue sections were deparaffinized by use of a microwave method and rehydrated. A panel of adequately diluted antibodies against AE1/AE3 (cytokeratin; BioGenex, San Ramon, Calif.), S-100 protein, vimentin, neuron-specific enolase, synaptophysin, chromogranin, glial fibrillary acidic protein, actin, p53 (Ab-6, pantropic; Oncogene-Calbiochem, Cambridge, Mass.), and retinoblastoma protein (Ab-5; Oncogene-Calbiochem) was investigated following the protocols recommended by the suppliers. The results showed immunoreactivity for cytokeratin, occasional immunoreactivity for S-100 protein, but lack of immunoreactivity for neuronspecific enolase, synaptophysin, vimentin, chromogranin, glial fibrillary acidic protein, and actin (data not shown). These results confirmed its epithelial origin and excluded the possibility of adenoid cystic carcinoma or neuroendocrine tumor. Meanwhile, there was strong expression of retinoblastoma protein in most cancer cells (Fig 3) but negative expression of p53 oncoprotein (data not shown). DISCUSSION Basaloid squamous cell carcinoma is a rare disease entity. Morphologically, it is composed of nests or sheets of basaloid cells with basophilic cytoplasm and uniform nuclei that show palisading arrangement at the periphery. It also contains areas of squamous cells with eosinophilic cytoplasm and keratinization.2,3,6,8 There are two types of tumors possessing these characteristics. One is basosquamous carcinoma of the skin,13,14 and the other is basaloid squamous cell carcinoma of the upper aerodigestive tract. In 1928 Montgomery13 named a skin tumor basal squamous cell epithelioma (carcinoma) on the basis of the histologic characteristics described as above. Borel14 and Schuller et al.15 each reported two series of the cutaneous basosquamous carcinoma. Comparison of the recurrence rate and metastatic rate among squamous cell carcinoma, basal cell carcinoma, and basosquamous carcinoma reached the same conclusions that the biologic behavior of the basosquamous carcinoma resembled that of squamous cell carcinoma, with both having a significant potential to recur and metastasize. Almost all of the basosquamous carcinomas were found on 647

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Fig 3. Retinoblastoma protein was strongly expressed in most cancer cells. (Immunostaining for retinoblastoma protein; original magnification ×66.)

Fig 1. Endoscopic view of a polypoid tumor located at the anterior part of left vocal cord with involvement of the anterior commissure.

Fig 2. Lobular solid nests of basaloid cells with focal adenoid cystic-like areas closely apposed to the surface mucosa. There are also scattered foci of conventional squamous cell carcinoma with keratin pearl formation within nests of basaloid cells. (Hematoxylin and eosin stain; original magnification ×66.)

the skin, and most of them were in the head and neck region. Montgomery believed that there were no true basosquamous carcinomas occurring in the mucous membrane. But Fresko and Lazarus16 reported a case of oral carcinoma progressed from squamous cell carcinoma to basosquamous carcinoma and basal cell carcinoma. Basaloid squamous cell carcinoma of the upper aerodigestive tract might be the mucosal counterpart of the cutaneous basosquamous carcinoma.

In 1986 basaloid squamous cell carcinoma of the upper aerodigestive tract was initially characterized by Wain et al.2 The characteristics of this tumor are solid growths of cells, with small, crowded cells and scanty cytoplasm; dark, hyperchromatic nuclei without nucleoli; small cystic spaces containing material resembling mucin that stained with periodic acid–Schiff (PAS), Alcian blue, or both. Central coagulative necrosis (comedonecrosis) and hyalinosis are also prominent features. The second histopathologic feature of this tumor is the intimate association of squamous cell carcinoma, dysplasia, or focal squamous differentiation with the basaloid tumor compartment. Wain et al. proposed that these tumors seemed to originate from the totipotent primitive cells located at the base of the pseudostratified columnar epithelium or the proximal salivary gland duct. Adenoid cystic carcinoma is the major differential diagnosis of this tumor. Positive immunoreactivity to antibodies against vimentin and S-100 protein and a lack of features characteristic of squamous cell carcinoma makes adenoid cystic carcinoma different from basaloid squamous cell carcinoma.2,8 The prognosis of basaloid squamous cell carcinoma is usually poor. This tumor is regarded as a biologically high-grade malignancy with a tendency toward locally aggressive behavior and early regional or distant metastases.2,3,6,8-11 This tumor has a predilection for the hypopharynx, tongue base, and larynx. Radical surgery followed by radiotherapy is the recommended treatment. Because of this tumor’s high incidence of distant metastases, ranging from 40% to 80%, systemic chemotherapy may be warranted.7,11 However, a study by Luna et al.5 revealed that the survival and incidence of cervical lymph node metastases paralleled those of conventional squamous cell carcinoma when the anatomic site, treatment, and clinical staging were matched. They also showed that aneuploid tumors had better mean survival time than those

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Table 1. Summary of previously reported basaloid squamous cell carcinomas of the larynx2-12 Authors

No. of cases

Location

Wain et al.2

3

All supraglottic

Shvili et al.4

1

Supraglottic

Tsang et al.6

4

All supraglottic

Gartlan et al.7 Banks et al.8 Klijanienko et al.9

1 8 2

Supraglottic — Both supraglottic

Larner et al.10 Raslan et al.11

1 2

Supraglottic Both supraglottic

Muller & Barnes12

1

Glottic

Sheen et al.

1

Glottic

Comments

2 patients died of multiple metastases; 1 patient was free of tumor 1.5 yr after supraglottic laryngectomy and radiotherapy Nasal tip metastasis 2.5 yr after total laryngectomy, partial pharyngectomy, radical neck dissection, and radiotherapy 1 patient was undergoing chemotherapy because of pulmonary metastasis 2.5 yr after total laryngectomy and radiotherapy; 1 patient was alive 1 yr after radiotherapy and then was lost to follow-up; 1 patient was alive 1 yr after radiotherapy and surgery; 1 patient committed suicide before treatment Treatment and outcome not given Location, treatment, and outcome not given 1 patient with lung metastasis was alive without disease 2.3 yr after surgery, radiotherapy, and chemotherapy; 1 patient with local metastasis was alive with disease 1 yr after surgery, radiotherapy, and chemotherapy Died of lung metastasis 2.5 yr after treatment 1 patient alive with disease 2 yr after surgery, radiotherapy and chemotherapy; 1 patient alive without disease 3 yr after surgery Patient had spindle cell component and was alive without disease 0.5 yr after total laryngectomy, neck dissection, and radiotherapy Alive without disease 13 years after partial vertical laryngectomy

with diploid carcinomas. But Raslan et al.11 could not confirm this prognostic prediction of DNA content from their series. For a definite conclusion, further study of additional cases is necessary. Twenty-three cases of basaloid squamous cell carcinoma of the larynx have been reported in the English language literature (Table 1). Most of them were large tumors of the supraglottis invading the tongue base or hypopharynx. Surgery followed by radiation, with or without adjuvant chemotherapy, was the most common modality of treatment. The outcomes were as poor as those for other basaloid squamous cell carcinomas arising in the head and neck. There has been only one reported case of glottic basaloid squamous cell carcinoma. Muller and Barnes12 reported this glottic type of tumor with spindle cell component in a 58-year-old man. He underwent total laryngectomy, left thyroidectomy, left modified radical neck dissection, and right zone VI lymphadenectomy because of a 3.2 × 2.4 cm glottic tumor with invasion to the subglottis and the overlying cervical strap muscles. He underwent postoperative radiotherapy and was free of disease after 6 months of followup. In our patient, because of the early stage (T1N0M0, stage I, UICC) and glottic location, a partial vertical laryngectomy was performed. He did not undergo postoperative radiotherapy because all of the surgical margins were free of tumor. His postoperative course was quite uneventful, and he has survived for 13 years with no sign of recurrence or metastasis. Both the retinoblastoma gene and p53 gene are tumor-suppressor genes that act as checkpoints in the cell cycle. No data are available regarding their expression in the basaloid squamous cell carcinoma. In this particular tumor, immunohisto-

chemistry showed no mutation of either tumor-suppressor gene product. In addition, the gross appearance of this tumor was quite different to that reported in previous studies. It presented as an exophytic, polypoid mass located at the anterior part of the left vocal cord, an area of sparse lymphatic drainage. All of these biologic characteristics might have contributed to the patient’s good outcome. CONCLUSION Although basaloid squamous cell carcinoma of the upper aerodigestive tract is aggressive, an early glottic type of tumor may be regarded as a different category and treated more conservatively, as demonstrated in this patient. We thank Ms. Chung-Chung Chen for her technical assistance in the immunohistochemistry. REFERENCES 1. Ferliot A. Histological classification of larynx and hypopharynx cancers and their clinical implications. Pathologic aspects of 2052 malignant neoplasms diagnosed at the ORL Department of Pudua University from 1966 to 1976. Acta Otolaryngol 1976; (suppl 342):1-88. 2. Wain SL, Kier R, Vollmer RT, et al. Basaloid-squamous carcinoma of the tongue, hypopharynx, and larynx: report of 10 cases. Hum Pathol 1986;17:1158-60. 3. Batsakis JG, el Naggar A. Basaloid squamous carcinoma of the upper aerodigestive tracts. Ann Otol Rhinol Laryngol 1989;98: 919-20. 4. Shvili Y, Talmi YP, Gal R, et al. Basaloid squamous carcinoma of the larynx metastatic to the skin of nasal tip. J Craniomaxillofac Surg 1990;18:322-4. 5. Luna MA, el Naggar A, Parichatikanond P, et al. Basaloid squamous carcinoma of the upper aerodigestive tract. Clinico-

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pathologic and DNA flow cytometric analysis. Cancer 1990; 66:537-42. Tsang WY, Chan JKC, Lee KC, et al. Basaloid-squamous carcinoma of the upper aerodigestive tract and so-called adenoid cystic carcinoma of the esophagus: the same tumor type? Histopathology 1991;19:35-46. Gartlan MG, Goetz SP, Graham SM. Basaloid-squamous carcinoma (BSC) of the larynx. Arch Otolaryngol Head Neck Surg 1992;118:998-1001. Banks ER, Frierson HF, Mills SE, et al. Basaloid squamous cell carcinoma of the head and neck. A clinicopathologic and immunohistochemical study of 40 cases. Am J Surg Pathol 1992; 16:939-46. Klijanienko J, el-Naggar A, Ponzio-Prion A, et al. Basaloid squamous carcinoma of the head and neck. Immunohistochemical comparison with adenoid cystic carcinoma and squamous cell carcinoma. Arch Otolaryngol Head Neck Surg 1993; 119:887-90. Larner JM, Malcolm RH, Mills SE, et al. Radiotherapy for basa-

11.

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loid squamous cell carcinoma of the head and neck. Head Neck 1993;15:249-52. Raslan WF, Barnes L, Krause JR, et al. Basaloid squamous cell carcinoma of the head and neck: a clinicopathologic and flow cytometric study of 10 new cases with review of the English literature. Am J Otolaryngol 1994;15:204-11. Muller S, Barnes L. Basaloid squamous cell carcinoma of the head and neck with a spindle cell component. An unusual histologic variant. Arch Pathol Lab Med 1995;119:181-2. Montgomery H. Dermatopathology. Vol 2. New York: Harper & Row; 1967. p. 934-40. Borel DM. Cutaneous basosquamous carcinoma. Arch Pathol 1973;95:293-7. Schuller DE, Berg JW, Sherman G, et al. Cutaneous basosquamous carcinoma of the head and neck: a comparative analysis. Otolaryngol Head Neck Surg 1979;87:420-7. Fresko D, Lazarus SS. Oral carcinoma in situ. Its progression to squamous, basosquamous, and basal-cell carcinoma. Arch Pathol Lab Med 1981;105:15-9.