Basaloid-squamous Cell Carcinoma of the Larynx and Hypopharynx

Basaloid-squamous Cell Carcinoma of the Larynx and Hypopharynx

Path . Res. Pract. 190, 186-193 (1994) Basaloid-squamous Cell Carcinoma of the Larynx and Hypopharynx~:- A Clinicopathologic Study of 7 Cases c. E...

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Path . Res. Pract. 190, 186-193 (1994)

Basaloid-squamous Cell Carcinoma of the Larynx and Hypopharynx~:-

A Clinicopathologic Study of 7 Cases


Ereno, J. I. Lopez, J. M. Sanchez 1 and J. D. Toledo

Departments of Pathology and lENT, Hospital de Basurto, Faculty of Medicine, Basque Country University (UPVIEHU), Bilbao, Spain

SUMMARY During a 16-)lear period (1974-1989), a retrospective review of 468 surgical specimens of laryngectomy yielded 7 cases (0.66 %) of basaloid-squamous cell carcinoma. They were all males between 42 and 63 years of age. Four cases were supraglottic and one transglottic. The other two arose in the left pyriform sinus and vallecula, respectively. At diagnostic time, 4 cases were Stage III and 2 Stage IV, only one being Stage II. Glanz index of histologic malignancy was high (> 5) in most cases (6/7). Mitotic rate was also high (22-78 mitosesllO HPF). Lymph node metastases were documented at diagnosis in 5 cases, 3 of them presenting with extracapsular extension. One case developed liver metastases. During the follow-up, lymph nodes of the neck were again metastasized in 4 cases, and stomal recurrence was present in another one. Death of disease was confirmed in 5 cases after 10 to 35 months of follow-up. Overall survival was 28.5 % after 3 years.

Introduction Basaloid-squamous cell carcinoma (BSCC) is quite a rare entity. It has been considered a distinct and specific histologic variant of squamous cell carcinoma that can be distinguished from other carcinomas on the basis of objective light microscopic criteria22 • The tumor mainly affects the upper aerodigestive tract, from where most cases have been referred to 1,2, 15-17, 19, 20,22,23 . Among them, there are only a few endolaryngeal examples 2,1 6, 19,20,22. Besides, this entity has been recently described in diverse locations such as lung4, anal canal6 and uterine cervix7, 18. In the present study we report the clinicopathologic features of 7 BSCC of the laryngeal region that were found in a retrospective review of carcinomas of the larynx. Literature concerning the topographic distribution, diag". This paper has been partially presented as a poster at the

XVI. Congress of the Spanish Society of Pathology (SEAP) (May 1993, Tenerife).


nostic criteria, differential diagnosis, and prognosis has been reviewed. Material and Methods During a 16-year period (1974-1989), an amoupt of 468 cases of carcinoma of the larynx were retrospectively reviewed in the Department of Pathology at the Hospital de BaslIrto, a tertiary care Medical Center affiliated to the Basque ·Country University that covers a population of 500,000 inhabitants in an industrial city of Northern Spain. Among them, 7 cases (0.66 %) fulfilled the histologic criteria of BSCC proposed by Wain et al.22. Signs and symptoms, clinical staging and follow-up of every case were obtained from medical records. All the cases were reexamined by at least two pathologists that assigned Stage and Grade accordantly. Pathologic staging was performed following the 1987 TNM c1assification 2 1, and Grade was given according to the score system proposed b yGlanz 8 . Mitotic count was assessed in a routinary manner [number of mitoses per 10 high power fileds (HPF, X40)) and tumor-associated tissue eosinophilia (TATE) evaluated following the method proposed by Goldsmith et aJ. 10. Survival was estimated by means of Kaplan-Meier curves 13 . © 1994 by Gustav Fischer Verlag, Stuttgart

Basaloid-sq uamo us Cell Carcinoma of the Larynx and Hypopharynx . 187

Results Clinical data and follow-up are summarized in Table 1. All the patients were males their ages ranging from 42 to 63 years (mean: 55.7). Hoarseness an d throat discomfort were the rnore frequent presenting symptoms. Four tumors were supraglottic (cases 4 to 7) and one transglottic (case 1). The others were situated in the vallecula (case 2)

and left pyriform sinus (case 3), respectively. All the cases were treated with total laryngectomy and lymph node dissection followed by adjuvant radiotherapy.

Pathological Findings Tumor size oscillated from 2 to 3.5 em in greatest diameter. Grossly, all the cases presented as flat, centrally

Table 1. Clinicopa thological findings of 7 basaloid-squamous cell carcinomas of the larynx a nd hypopharynx Case








1 2 3 4 5 6 7

49 62 42 63 63 50 61


Transglotti c Vallecula Left pyrifo rm Supraglottic Supraglottic Supraglottic Supraglottic

3 1 3 3 3 2 3

1 2 2 1 1 0 0


DOD, DOD, DOD, DOD, DOD, Alive, Alive,

10m 35 m 18 m 25 m 15 m 49 m 39 m

DOD: Dead of disease (in months)

Fig. 1. Panoramic view shows large neoplastic nests composed of basaloid and squamous cells situated between the surface squamous epithelium and the epiglottic cartilage. (H&:E, x40).

Fig. 2. Panoramic view shows small neoplastic nests of basaloid appearance hanging from the surface squamo us epithelium. Microcystic change and fibrous stroma with lymphoid infiltrate are also seen. (H&E, x40).

188 . C. Ereno et al.

Fig. 3. Basaloid nests with peripheral palisading are seen within a hyaline stroma. Squamous cells center some basaloid islands . (H&E, X 100).

Fig. 4. Basal-type cells sometimes display an adenoid cystic appearance. (H&E, XIOO).

Table 2. Wain's criteria in primary tumors (7 cases) Case

Basaloid component Solid growth Cellularity Nuclei Cystic spaces Necrosis Hyalinosis Squamous component Keratinization Intercellular bridging Horny pearls Mosaic pattern








+++ +++ +++ + +++ +++

++ ++ ++

+++ +++ +++ +++ +++ +

++ +++ +++

++ +++ +++ +++ + +

+++ ++ ++

+++ +++ +++ +++ +++ +++





+ + + +

++ ++ ++ ++

++ ++ ++ ++

++ +++ ++ + ++

+ + + +

+ ++

Basaloid-squamous Cell Carcino ma of the Larynx a nd H ypopharynx· 189

ulcerated tumors. Pathologic staging at diagnosis displayed advanced disease in 6 cases, 4 of them being Stage III (cases 1,4,5 and 7) and 2 Stage IV (cases 2 and 3) . Only one case was Stage II (case 6) (Table 1). Microscopically, all the tumors displayed the characteristic biphasic pattern, with basaloid and squamous areas (Figs. 1 and 2). Table 2 summarizes the distribution of Wain's criteria. Basaloid areas were more abundant and showed solid islands, anastomosing trabecula and microcystic structures (Figs. 2 and 3) . This last finding was extensively seen in cases 3,5 and 7 (Table 2). Proliferating basal cells showed their typical appearance with high mitotic index (22 to 78 mitoses/lO HPF), peripheral nuclear palisading, and adenoid cystic-like structures (Fig. 4). Central necrosis of comedo type was occasionally evidenced in cases 1,3 and 7 (Fig. 5). The relative amount of the squamous component varied greatly. Case 1 revealed severe dysplasia in the ad jacent mucosa. Every case showed areas with carcinoma in situ and zones with an infiltrating pattern. Usually, proliferating squamous cells displayed mild to moderate atypia, mitoses were scanty, and keratinization evident. Noteworthy, "horny pearls" showed a tendency to center basaloid nests, giving

T able 3. Histo logical ma ligna ncy index of Glanz

Fig. 5. Peripheral palisading and central comedo-rype necrosis are occasionally seen in basaloid nests. (H&E, X 100).

Fig. 6. High power view shows occasional "horny pearls" into basaloid nests. (H&E, x400).



1 2 3 4 5 6




Vasclperin Inv

Cell response



2 1 2 2 2


8 6

3 3 3

1 2 2


1 1




a 0




1 2 0

9 8

7 5 3

grade : Grade of differentiation and tumor polymorphism; border: Tumor border, expansive versus infiltrative; vasclperin inv: Vascular and/or perineurial invasion; cell response: Cellular response of rhe host (inflammation).

rise to mixed, basaloid/squamous, islands (Fig. 6). As a whole, keratinization was scanty in 4 cases and moderate in 3. Tumor edges were of expansive nature in 4 cases and infiltra tive in the rest (Table 3) . A highly h yalinized stroma was seen in 5 cases, sometimes displaying pericellular

190 . C. Ereno et al.

Fig. 7. Hyaline fibrosis displays a pericellular arrangement in some areas. (H&E, x400).

Fig. 8. Metastases to regional lymph nodes display both basaloid (up) and squamous (bottom) components. (H&E, x40).

eosinophilic condensations (Fig. 7). Perineurial invasion was demonstrated in 5 cases. A prominent cellular response of the host was present in 4 cases. Table 3 also summarizes the result of the scoring system proposed by Glanz for the assessment of malignancy. TATE was considered as grade 0 in two examples (cases 1 and 2), grade 1 in one (case 4), grade 2 in one (case 7), grade 3 in one (case 3), and grade 4 in two (cases 5 and 6). Noticeably, the amount of eosinophils was specially pronounced at the edge of well keratinized squamous islands. At diagnostic time, 5 cases presented with lymph node metastases (3 cases were pN1 and 2 pN2) (Table 1). Node metastases showed extracapsular extension in cases 1,3 and 5. In addition, one case (case 2) revealed metastases to the liver. Interestingly, the metastatic seed somehow recapitulated the biphasic pattern observed in primary tumors (Table 4) (Fig. 8). Cases 1 and 2 mainly displayed basaloid areas and case 3 additionally showed adenoid cyst-like structures (Fig. 9). The squamous component predominated in case~, 3 and 4. Case 5 showed similar proportions of both basaloid and squamous components.

Table 4. Wain's criteria in lymph node metastases (5 cases) Case

Basaloid component Solid growth Cellularity Nuclei Cystic spaces Necrosis Hyalinosis Squamous component Keratinization Intercellular bridging Horny pearls M.osaic pattern




+++ +++ +++ + +++ +++

+++ +++ +++ + +++ +

+ +

+ + + + +++ +

++ ++ +++ ++ +++ +





++ ++ +++ +++

++ ++ ++ ++


++ ++ ++ ++


Follow-up Data Follow-up ranged from 10 to 49 months. Four patients developed cervical lymph node metastases 6 to 22 months

Basaloid-squamous Cell Carcinoma of the Larynx and Hypopharynx . 191


1 .

........ 1 :29 . .. · .. 1 I",,,,,,!





,......·.... ·.......... ·1



+--+__I+·· · ·_·-+__···r-__


60 m.

Fig. 10. Survival curve of basaloid-squamous cell carcinomas of the larynx and hypopharynx (Kaplan-Meier).

Fig. 9. High power view of a metastatic node showing adenoid cystic-like arrangement. (H&E, x400).

after surgery and one, recurrence in the stoma. As a whole, 5 patients died of tumor between 10 and 35 months after surgery. The other two patients were lost for follow up after 39 and 49 months, respectively. Overall 3-year survival was estimated to be 28.5 % (Fig. 10). In our experience, the comparison of survival curves of BSCC and squamous cell carcinomas of the larynx at the same Stage and Grade, by the log-rank test, did not display any significant difference. Discussion In spite of the fact that the overwhelming majority of laryngeal neoplasms are squamous cell carcinomas24, some histologic variants with presumpted prognostic implications have been identified in recent years 3 • Among them, BSCC was first described in 1986 by Wain et al. 22 as a distinctive clinicopathologic entity. As a matter of fact, it is a rare tumor that has well defined histology and immunophenotype, and that seems to pursue an aggressive course 2,4,16,20,22.

Previously reported cases of BSCC of the upper aerodigestive tract show a strong tendency to occur in extralaryngeal sites such as pyriform sinuses and base of tongue 2,16,17,19,20. Endolaryngeal cases have been less frequently reported. In this sense, Banks et al. 2 present 8 cases that represent the largest series ever published, but the authors do not specify the exact laryngeal compartment where the tumors arose. In the present series, 5 out of 7 cases were endolaryngeal, supraglottis being the site of preference. As usual, smokers males in their late fifties and sixties predominate2,16,20,22. We have failed to demonstrate any difference in the clinical manifestations between these patients and those bearing conventional squamous cell carcinomas. Since the series of Wain et al. 22 , BSCCs at any topography have been considered highly aggressive and metastasizing neoplasms. Banks et al. 2 report lymph node and even distant metastases in 75 % of cases at diagnosis. In fact, we have observed advanced disease (Stages III and IV) at diagnosis in 6 out of 7 cases and lymph node metastases in 5. What is more, the extension of the tumor beyond the lymph node capsule - a histological feature considered of ominous prognosis in laryngeal cancer 12 - has been documented in 3 of our cases. However, we agree with Luna et al,16 in that no statistical differences of survival are seen when comparing BSCC with conventional squamous cell carcinomas at the same Stage, Grade, and topography. On gross examination, most BSCC are flat or slightly elevated tumors with a central ulceration l6 . Although this tumor has been occasionally diagnosed by fine needle aspiration cytologyl, the histological recognition of its peculiar features 22 remains as the sole reliable diagnostic method. Some features are quite specific, for example, basaloid nests with high mitotic index hanging from the surface epithelium2o , squamous pearls centering basaloid nests, hyaline stroma sometimes with pericellular distribution I6 ,20,22, and comedo type necrosis. Less specific are expansive edges and inflammatory response of the host. T ATElo, a parameter that has not been previously eva-

192 . C. Ereno et al.

luated in these tumors, seems to us to affect preferentially the borderland between keratinized nests and stroma. The differential diagnosis of BSCC mainly includes neuroendocrine, mucoepidermoid, adenosquamous, and adenoid cystic carcinomas. Actually, some neuroendocrine can:inomas composed by intermediate-type cells can eventually display a submucous arrangement with basaloidappearing nests 9 . This feature together with the occasional finding of foci of squamous metaplasia can make the correct diagnosis a difficult task. The expression of basal cell-type cytokeratins favour the diagnosis of BSCO. On the other hand, positivity for neuroendocrine markers 9 and the demonstration of neurosecretory granules on ultrastructure support a neuroendocrine nature. To be noticed, this differential diagnosis carries crucial therapeutic implications 2. Finally, solid variants of the adenoid cystic carcinoma 2,16,20,22, high grade mucoepidermoid carcinomas and adenosquamous carcinomas 16 can in fact be excluded if one strictly applies the diagnostic criteria of BSCC22. The histogenesis of BSCC of the larynx has been a permanent matter of debate. Based on ultrastructural and immunohistochemical findings, some authors 4,20,22 propose that these tumors derivate from a totipotential stem cell with capacities to differentiate toward divergent cell lines. But what these authors do not comment at all are other more explicit questions related with the peculiar topographic distribution that BSCCs often display. Amazingly, most of these tumors originate from tissues derived from either rostral (estomodeum) or caudal (proctodeum) parts of the primitive digestive tube. As a matter of fact, there are reported cases of BSCC from the larynx 2, 19,22, hypopharynx 2, 16, 17, 19,22, esophagus 20 , base of tongue 2,16,22, tonsiF, palate 15 and nasal cavity2,23, but also from the anal canal6 and uterine cervix?, 18. It should be noticed that both regions are borderland territories in which endodermal and ectodermal fields meetS, so the strong tendency BSCCs show to arise in these frontiers could be more than casual. With regard to the cases arising within the larynx, there is also an interesting observation that has received little attention in the literature. Most en do laryngeal cases in which the exact origin is specified demonstrate that BSCCs are mainly supraglottic tumors20,22. Actually, 4 out of our 5 endolaryngeal cases are like that. Again this fact could be more than casual, for the supraglottis has a different embryologic origin from the rest of the larynx l l ,14. Interestingly, this origin coincides with that of hypopharynx, i.e., the bucopharyngeal anlage (third and fourth visceral arches) 14. To summarize, BSCCs are rare and aggressive tumors with a peculiar topographic distribution, usually related to the upper aerodigestive tract. Despite their presumpted aggressiveness, we have not demonstrated that BSCC behave worse than squamous cell carcinomas not otherwise specified. In our experience, just a careful search of its histological criteria must allow the correct diagnosis in most cases. Immunohistochemistry and ultrastructure can be of aid mainly in its differential diagnosis and also in selected cases presenting a troublesome histology.

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Basaloid-squamous Cell Carcinoma of the Larynx and Hypopharynx . 193 and so-called adenoid cystic carcinoma of the oesophagus: the same tumour type? Histopathology 19: 35--46 21 UICC (1987) TNM Classification of malignant tumours. Hermanek P, Sobin LH (Eds), 4th edition. Springer-Verlag, Berlin 22 Wain SL, Kier R, Vollmer RT, Bosen EH (1986) Basaloid squamous carcinoma of the tongue, hypopharynx, and larynx: Report of 10 cases. Hum Pathol17: 1158-1166

23 Wan SK, Chan JKC, Tse KC (1992) Basaloid-squamous carcinoma of the nasal cavity. L Laryngol Otol 106: 370-371 24 Wiernik G, Millard PR, Haybittle JL (1991) The predictive value of histological classification into degrees of differentiation of squamous cell carcinoma of the larynx and hypopharynx compared with the survival of patients. Histopathology 19: 1]-17

Received September 1, 1993 . Accepted in revised form October 5, 1993

Key words: Basaloid-squamous cell carcinoma - larynx - hypopharynx - Differential diagnosis Prof. Juan D. Toledo, Dept. de Anatomia Patol6gica, Hospital de Basurto, Avda. de Montevideo 18,48013 Bilbao, Spain