Squamous cell carcinomas account for over 90% of all laryngeal carcinomas. As of 1997, there were 10,990 new cases reported in the United States. The tumor is divided by the three divisions of the larynx. Under the microscope, these tumors have features similar to squamous cell carcinomas arising in other organs. The pathologist must clearly define the extent of the tumor and carefully check the regional lymph nodes to exclude a metastases. Early changes of cancer are denoted as dysplasia and may lead to invasive cancer. Most pathologists utilize a three tiered system of grading dysplasia. In general, dyskeratotic cells may be an important clue to the diagnosis.
Epidemiology Disease Associations Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/
Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
DISEASE ASSOCIATIONS CHARACTERIZATION LARYNGEAL PAPILLOMATOSIS
Molecular events in the progression of recurrent respiratory papillomatosis to carcinoma.
Lele SM, Pou AM, Ventura K, Gatalica Z, Payne D.
Department of Pathology, University of Kentucky College of Medicine, Lexington (Dr Lele); and the Departments of Otolaryngology (Drs Pou and Payne) and Pathology (Drs Ventura, Gatalica, and Payne), The University of Texas Medical Branch at Galveston.
Arch Pathol Lab Med 2002 Oct;126(10):1184-8 Abstract quote
Context.-Identification of the type of human papillomavirus (HPV) by polymerase chain reaction and sequencing to determine coinfection or superinfection (by more than 1 HPV type) and other molecular events have not been reported in a series of patients exhibiting the morphologic spectrum of recurrent respiratory papillomatosis progressing to carcinoma.
Design.-Four cases of juvenile-onset recurrent respiratory papillomatosis progressing to carcinoma (no history of smoking or irradiation in 2 cases) were studied. Morphologically distinct foci (squamous papilloma, pulmonary papillomatosis, squamous dysplasia subjacent to carcinoma, and squamous carcinoma) were subjected to laser capture microdissection and polymerase chain reaction amplification using general primers in addition to type-specific primers for HPV types 16 and 18. Direct sequencing of polymerase chain reaction products identified the type of HPV. The tissue sections were immunostained using antibodies to p53, pRb, p21(WAF1), and p16 proteins with a semiquantitative assessment.
Results.-Human papillomavirus 11 was the only type of HPV identified in all lesions of all cases associated with recurrent respiratory papillomatosis. There was a marked increase in p53 protein expression in foci of dysplasia and carcinoma as compared to squamous papilloma and pulmonary papillomatosis. An inverse correlation between p53 and p21(WAF1) protein expression was noted in all lesions. pRb protein expression increased from the benign to the malignant end of the spectrum. p16 protein was expressed in all lesions.
Conclusions.-Infection by HPV-11 may be an early event associated with progression of recurrent respiratory papillomatosis to carcinoma. Increased expression of p53 and pRb proteins and a reduced expression of p21(WAF1) protein appear to be significant subsequent events.
PATHOGENESIS CHARACTERIZATION COX-2
Overexpression of cyclo-oxygenase 2 in squamous cell carcinoma of the hypopharynx
Jyh-Ping Peng, MD
Chih-Ying Su, MD
Hui-Chiu Chang, PhD
Chee-Yin Chai, MD, PhD
Wen-Chun Hung, PhD
Hum Pathol 2002;33:100-104. Abstract quote
Upregulation of cyclo-oxygenase 2 (COX-2) expression is frequently found in a variety of human cancers.
In this study, we examined COX-2 expression in squamous cell carcinoma of the hypopharynx. COX-2 messenger RNA (mRNA) analyzed by reverse-transcription polymerase chain reaction was detected in 87% (20 of 23) of tumor tissues. Expression of COX-2 protein was examined by Western blot analysis. COX-2 protein levels were increased in tumor tissues and correlated with the expression level of mRNA. Immunohistochemical study was performed to detect the subcellular localization of COX-2. Our results showed that COX-2 was predominantly detected in cancer cells, and the staining pattern was cytoplasmic. Several histologically normal adjacent tissues obtained from these patients were also investigated.
We found that COX-2 mRNA was detectable in these tissues. However, COX-2 mRNA and protein levels were lower in these tissues than in tumor specimens. In contrast, COX-2 mRNA and protein levels in normal oral mucosa obtained from healthy volunteers were very low or undetectable. The frequency of COX-2 overexpression was significantly higher in the N1-N3 group than in the N0 group.
These results suggest that overexpression of COX-2 is linked with increased lymphatic invasion in hypopharyngeal carcinoma. Collectively, these results suggest that overexpression of COX-2 is a frequent phenomenon in hypopharyngeal carcinoma and may play a role in tumorigenesis of this cancer.
Prognostic significance of cyclooxygenase-2 pathway and angiogenesis in head and neck squamous cell carcinoma.
Gallo O, Masini E, Bianchi B, Bruschini L, Paglierani M, Franchi A.
Department of Oto-Neuro-Ophthalmologic Surgery, University of Florence Medical School, Florence, Italy.
Hum Pathol 2002 Jul;33(7):708-14 Abstract quote
Prostaglandins play a critical role in tumor development and growth by regulating numerous biologic processes, including tumor angiogenesis, with clear prognostic and therapeutic implications.
The aim of this study was to investigate the prognostic relevance of cyclooxygenase-2 (COX-2) pathway activation in head and neck squamous cell carcinoma (HNSCC). COX-2 activity was analyzed in 52 consecutive patients by assessing protein expression and prostaglandin E(2) (PgE(2)) levels and was then correlated to vascular endothelial growth factor (VEGF) expression and tumor angiogenesis. We evaluated the prognostic impact of these parameters by Kaplan-Meier and Cox survival analysis. COX-2 expression by tumor cells was closely correlated to VEGF expression and to tumor vascularization. According to Kaplan-Meier analysis, patients with COX-2 tumor overexpression and with higher PgE(2) tumor levels had significantly shorter overall survival estimates (P = 0.022 and P = 0.033, respectively). Analogously, patients with more-vascularized tumors had worse survival than those with less-vascularized cancers (P = 0.032). Cox multivariate analysis demonstrated that the most significant prognostic factors were presence of lymph node metastasis, tumor vascularization, COX-2 protein expression, and PgE(2) tumor levels.
This study demonstrates a close correlation between COX-2 pathway, VEGF expression, and tumor angiogenesis in HNSCC. In addition, COX-2 overexpression and higher tumor vascularization appear to predict a shorter survival in patients with head and neck cancer.
- Human papillomavirus and Epstein-Barr virus infection, p53 expression, and cellular proliferation in laryngeal carcinoma. de Oliveira DE, Bacchi MM, Macarenco RS, Tagliarini JV, Cordeiro RC, Bacchi CE.
Department of Pathology, Botucatu School of Medicine at Sao Paulo State University, Sao Paulo, Brazil.
- Am J Clin Pathol. 2006 Aug;126(2):284-93. Abstract quote
Laryngeal carcinomas are aggressive neoplasms with controversial association with the human papillomavirus (HPV) and Epstein-Barr virus (EBV). So far, the impairment of p53 protein function and its impact on cellular proliferation has not been studied adequately in these tumors.
In this work, molecular biologic techniques were used to assess the frequency of HPV and EBV in 110 squamous cell carcinomas of the larynx. In addition, accumulation of p53 and Ki-67 cell proliferation antigen expression in malignant cells was assessed by immunohistochemical analysis. High-grade HPV was found in 37.3% of cases, and none had demonstrable EBV infection. Accumulation of p53 was found in 78.2% of the cases, and it was related to a high Ki-67 labeling index and higher histologic grade.
The results demonstrate association of HPV with more than one third of laryngeal carcinomas studied, mainly glottic tumors. Tumors with increased cell proliferation were more frequently high grade, with p53 accumulation and lymph node metastasis.
Immunohistochemical p53 Expression Patterns in Sarcomatoid Carcinomas of the Upper Respiratory Tract
M. Ali Ansari-Lari, M.D., Ph.D.; Mohammad O. Hoque, D.D.S., Ph.D.; Joseph Califano, M.D.; William H. Westra, M.D.
Am J Surg Pathol 2002; 26(8):1024-1031 Abstract quote
Sarcomatoid carcinoma of the upper respiratory tract is a phenotypically complex neoplasm that has triggered much thoughtful discussion regarding histogenic origin and morphologic classification. In particular, its putative epithelial lineage and distinction from a pseudosarcomatous reaction are sometimes questioned. Little is known about the genetic alterations underlying sarcomatoid carcinoma. Although about 45% of conventional squamous cell carcinomas of the upper respiratory tract harbor p53 mutations, the p53 status of sarcomatoid carcinomas is not well established.
p53 immunohistochemical analysis using the monoclonal antibody D07 was performed on 23 sarcomatoid carcinomas of the upper respiratory tract. Twenty tumors were biphasic, having dual epithelial and spindled components. In four of these biphasic tumors, the epithelial and spindled components were separately analyzed for p53 gene mutations by sequence analysis. p53 immunohistochemistry was also performed on 19 cases of postradiation stromal atypia. Strong and diffuse p53 staining was detected in 18 (78%) of the 23 sarcomatoid carcinomas.
When the spindled component was compared with its corresponding epithelial component, identical patterns of p53 protein expression were noted in 19 (95%) of the 20 biphasic tumors. Weak p53 staining was observed in one (5%) of the 19 cases of postradiation stromal atypia. In the four biphasic tumors evaluated by DNA sequence analysis, p53 status was always the same in the paired epithelial and spindle cell components.
These findings help further dispel the notion that sarcomatoid carcinoma represents a reactive spindle cell proliferation (pseudosarcoma) or a collision between a carcinoma and a sarcoma (collision tumor). Instead, the epithelial and spindled components share a common pathway of tumorigenesis despite their conspicuous divergence at the phenotypic level.
Induced expression of syndecan-1 in the stroma of head and neck squamous cell carcinoma.
Mukunyadzi P, Liu K, Hanna EY, Suen JY, Fan CY.
Department of Pathology, University of Arkansas for Medical Sciences and Central Arkansas Veterans Healthcare System, Little Rock, Arkansas 72205, USA.
Mod Pathol. 2003 Aug;16(8):796-801 Abstract quote
Syndecan-1 (CD138), a cell-surface heparan sulfate proteoglycan, is involved in cell-cell, cell-matrix interaction and growth factor binding. Loss of expression of syndecan-1 in tumor cells leads to decreased intercellular cohesion, increased potential for tumor invasiveness, and metastatic spread. Furthermore, induction of syndecan-1 expression in the tumor stroma has been postulated to promote tumor angiogenesis via its binding to growth factors such as basic fibroblast growth factor. Although syndecan-1 expression within tumor cells has been investigated in head and neck squamous cell carcinoma, stromal expression has not been studied in detail.
We analyzed 38 cases of head and neck squamous cell carcinoma by immunohistochemical staining for syndecan-1 expression within the stroma. The expression of syndecan-1 within tumor cells of various histologic grades of differentiation, squamous cell carcinoma in situ cells, and benign squamous epithelium was also determined. Variable levels of diminished syndecan-1 expression were noted within the dysplastic cells of 9 of 16 (60%) squamous cell carcinoma in situ lesions and in all 38 (100%) invasive squamous cell carcinoma. In general, higher levels of syndecan-1 expression were observed in the well-differentiated tumors, in contrast to significant reduction of expression seen in poorly differentiated tumors. Syndecan-1 expression was observed within the stroma (in fibroblasts) surrounding infiltrating carcinoma cells in 28 of 38 (74%) cases. The intensity of syndecan-1 staining within the stroma showed generally an inverse correlation with the degree of tumor cell differentiation. Syndecan-1 expression was not detected in the stroma beneath normal squamous epithelium or adjacent to areas of squamous cell carcinoma in situ.
We conclude that induced expression of syndecan-1 in the stroma surrounding tumor cells of invasive head and neck squamous cell carcinoma is a frequent event. The increased stromal syndecan-1 expression, coupled with its loss from the surface of carcinoma cells, may contribute to tumor cell invasion and the development of metastases.
TELOMERASE CATALYTIC SUBUNIT
- Telomerase catalytic subunit in laryngeal carcinogenesis-an immunohistochemical study.
Luzar B, Poljak M, Gale N.
1Institute of Pathology, Medical Faculty University of Ljubljana, Ljubljana, Slovenia.
Mod Pathol. 2005 Mar;18(3):406-11. Abstract quote
We recently demonstrated that (1) telomerase catalytic subunit messenger RNA (mRNA) relative quantities increase progressively with the degree of laryngeal epithelial abnormalities and that (2) telomerase catalytic subunit gene re-expression represents an early event in laryngeal carcinogenesis.
The aim of the study was to determine whether telomerase catalytic protein immunohistochemisty reflects telomerase catalytic subunit gene expression in different grades of laryngeal epithelial abnormalities and squamous cell carcinomas of the larynx. Telomerase catalytic protein was analysed immunohistochemically in 106 laryngeal epithelial tissue samples: 10 normal epithelia, 15 squamous cell hyperplasias, 14 basal/parabasal cell hyperplasias, 10 atypical hyperplasias, eight intraepithelial carcinomas and 49 squamous cell carcinomas.
At least 200 nuclei of each lesion were quantified per slide and the number of positive signals per nucleus was expressed as a telomerase catalytic protein index. The mean telomerase catalytic protein index increased progressively with the degree of laryngeal epithelial abnormalities: from 0.17 in normal epithelia, 0.44 in squamous cell hyperplasia, 0.54 in basal/parabasal cell hyperplasia, 0.91 in atypical hyperplasia, 1.05 in intraepithelial carcinoma to 0.96 in squamous cell carcinomas.
Statistical analysis revealed three different groups of laryngeal epithelial changes according to the number of telomerase catalytic protein signals per nucleus: (1) normal epithelium, (2) regenerative epithelium (squamous cell hyperplasia, basal/parabasal cell hyperplasia), and (3) atypical hyperplasia, intraepithelial carcinoma and squamous cell carcinoma (P<0.0033). Telomerase catalytic protein immunohistochemistry parallels well with telomerase catalytic subunit mRNA relative quantities in laryngeal carcinogenesis.
In normal and regenerative laryngeal epithelia, telomerase catalytic protein is present in occasional basal/parabasal nuclei, becomes undetectable with maturation or differentiation of epithelial cells, and reflects the regenerative capacity of squamous epithelium. Nevertheless, several telomerase catalytic protein signals in the majority of nuclei in precancerous lesions, intraepithelial carcinomas and squamous cell carcinomas, are consistent with telomerase catalytic subunit gene re-expression, an early event in laryngeal carcinogenesis.
CLINICAL VARIANTS CHARACTERISTICS Glottic
(True vocal cord)
T1-confined to level of free edge of vocal cord
T2-Extends below cord with mobility maintained or limited
T3-Fixed cord with invasion of the thyroarytenoid muscle
Supraglottic May arise in epiglottis, ventricular band, aryepiglottic fold, or arytenoid body Transglottic Cancer crosses the ventricle and associated with a fixed vocal cord
Metastases to cervical lymph nodes likely in tumors >4 cm
Carcinoma of the pyriform sinus: a retrospective analysis of treatment results over a 20-year period.
Elias MM, Hilgers FJ, Keus RB, Gregor RT, Hart AA, Balm AJ.
Department of Otolaryngology-Head & Neck Surgery, The Netherlands Cancer Institute, Amsterdam.
Clin Otolaryngol 1995 Jun;20(3):249-53 Abstract quote
One hundred and one patients with pyriform sinus carcinoma treated at the Netherlands Cancer Institute were studied retrospectively.
The patients were staged according to the UICC criteria of 1987: there were no stage I, 23 stage II, 30 stage III, and 48 stage IV patients. The treatment consisted of radiotherapy (n = 45), a planned combination of surgery and post-operative radiotherapy (n = 47) or surgery alone (n = 9). The crude 5-year survival was 27%, whereas the 5-year disease-free survival was 37%. The locoregional disease-free survival was 52%.
Stage according to the UICC 1987 criteria is an important prognostic variable (P = 0.0026).
Furthermore, significantly less locoregional recurrences and a better disease-free survival were seen in the combined surgery and radiotherapy group than in the exclusively irradiated group (P < 0.0001).
HISTOLOGIC VARIANT DESCRIPTION DYSPLASIA GRADE HISTOLOGIC CRITERIA Mild Nuclear irregularity with nuclear crowding within the basal layer Moderate Larger, irregular nuclei, peripherally condensed chromatin, focally prominent nucleoli
Mitotic figures within the basal layer
Severe (Encompasses carcinoma in situ) Aberrant cell maturation with dyskeratotic cells
Mitotic figures above the basal layer
Atypical mitotic figures
VARIANTS ADENOSQUAMOUS CARCINOMA
Adenosquamous carcinoma of the upper aerodigestive tract: a clinicopathologic study of 12 cases and review of the literature.
Keelawat S, Liu CZ, Roehm PC, Barnes L.
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Am J Otolaryngol 2002 May-Jun;23(3):160-8 Abstract quote
PURPOSE: Adenosquamous carcinoma is an uncommon, controversial neoplasm. To further comprehend its natural history, the clinical and pathological features of 12 new cases were reviewed and analyzed collectively with those described in the English literature.
MATERIALS AND METHODS: Twelve cases of adenosquamous carcinoma of the upper aerodigestive tract with adequate follow-up and available microscopic slides and paraffin tissue blocks were identified in the anatomic pathology files of Presbyterian Hospital of the University of Pittsburgh Medical Center over the period 1983-2001.
RESULTS: The 8 men and 4 women ranged in age from 34 to 81 years (mean, 62.8 years). The larynx (5 cases) and the floor of the mouth (4 cases) were the most common sites of origin. Nine patients had cervical lymph nodes positive for carcinoma (8 at diagnosis), 7 experienced local recurrences, and 2 developed distant metastases. Four of 10 (40%) patients with follow-up died of disease. Combining our cases with those in the literature (total of 58 cases) revealed similar findings: 64.7% were associated with positive cervical lymph nodes, 46.7% experienced local recurrences, 23.1% developed distant metastases, and 42.9% died of their disease at a mean follow-up period of 24.7 months.
CONCLUSIONS: Adenosquamous carcinoma is an aggressive neoplasm with a tendency for early lymph node metastasis, frequent local recurrence, occasional distant metastasis, and death from disease, usually within 2-3 years. Surgery with neck dissection is the treatment of choice.
BASALOID SCC High grade variant of squamous cell carcinoma usually presenting with advanced clinical stage and is associated with poor prognosis COMBINED
- Primary combined squamous and small cell carcinoma of the larynx: a case report and review of the literature.
Jaiswal VR, Hoang MP.
Department of Pathology, The University of Texas Southwestern Medical Center, Dallas 75390-9073, USA.
Arch Pathol Lab Med. 2004 Nov;128(11):1279-82. Abstract quote
Primary laryngeal carcinomas comprise approximately 2% to 5% of all malignancies worldwide. Of these laryngeal carcinomas, approximately 99% are primary squamous cell carcinomas.
During the past 30 years, about 160 cases of primary small cell carcinoma of the larynx have been reported. Combined primary squamous and small cell carcinoma of the larynx, the so-called composite tumor of the larynx, is even more rare, with only 13 published cases to date. Although the major risk factors for developing these composite tumors of the larynx are thought to be similar to other more common neoplasms of the larynx, such as squamous cell carcinoma, the treatment and prognosis are different.
We report an additional case of combined small cell carcinoma of the larynx and discuss the histogenesis of this unusual neoplasm.
SARCOMATOID SCC These tumors may represent a reactive pseudosarcomatous stromal change, a spindled or sarcomatous squamous cell carcinoma, or a true sarcoma arising with a squamous cell carcinoma Spindle Cell (Sarcomatoid) Carcinomas of the Larynx
A Clinicopathologic Study of 187 Cases
Lester D. R. Thompson, M.D. ; Jacqueline A. Wieneke, M.D. ; Markku Miettinen, M.D. ; Dennis K. Heffner, M.D.
From the Departments of Endocrine and OtorhinolaryngicHead & Neck Pathology (L.D.R.T., J.A.W., D.K.H.) and Soft Tissue Pathology (M.M.), Armed Forces Institute of Pathology, Washington, DC, U.S.A.
Am J Surg Pathol 2002;26:153-170 Abstract quote
Laryngeal spindle cell (sarcomatoid) carcinomas are uncommon tumors, frequently misdiagnosed as reactive lesions or mesenchymal malignancies.
The records of 187 patients with tumors diagnosed as laryngeal spindle cell (sarcomatoid) carcinoma were retrieved from the files of the Otorhinolaryngic Tumor Registry of the Armed Forces Institute of Pathology.
There were 174 men and 13 women, 3592 years of age (average, 65.6 years). Nearly all patients experienced hoarseness (n = 165 [88%] patients) for a mean duration of 11.0 months. Patients admitted to smoking (n = 162 [87%] patients) and/or alcohol use (n = 90 [48%] patients). Most tumors were glottic (n = 132 [71%]), T1 (n = 111 [59%]), 1 and polypoid (n = 185 [99%]), with a mean tumor size of 1.8 cm.
Histologically, squamous cell carcinoma (n = 157 [84%]) was noted, ulcerated, and blended with the spindle cell component, which was most frequently arranged in a storiform pattern (n = 92 [49%] tumors). Foci of benign or malignant cartilage and/or bone (n = 13 [7%]) were noted in the spindle cell component.
All patients were treated with surgery (n = 90 [48%] patients) or surgery with radiation (n = 97 [52%] patients). Recurrences developed in 85 (45%) patients.
Overall, T1 glottic tumors managed by complete surgical eradication had the best outcome (mean follow-up, 7.8 years).
SMALL CELL (NEUROENDOCRINE) VERRUCOUS CARCINOMA Large exophytic tumors with only mild cytologic atypia but may be localy aggressive
Validation of tissue microarrays using p53 immunohistochemical studies of squamous cell carcinoma of the larynx.
Griffin MC, Robinson RA, Trask DK.
Department of Otolaryngology/Head and Neck Surgery, University of Iowa Health Care, Iowa City, Iowa 52242, USA.
Mod Pathol. 2003 Dec;16(12):1181-8. Abstract quote
Tissue microarrays are a powerful new tissue-conserving technology in the study of cancer, allowing simultaneous study of a large number of tumor specimens.
We sought to ascertain the utility of tissue microarrays in head and neck cancer pathology using squamous cell carcinoma of the larynx as a model system. Whole-specimen slides from 44 different laryngeal squamous cell carcinomas were stained for p53 expression. Microarrays were then generated by taking six 0.6-mm core biopsies from each of the 44 specimens. The whole sections and the microarrays were independently scored for p53 expression. Twenty-three (53%) of the 44 tumor specimens were positive for p53. Forty-four of the 264 core biopsies (17%) were not given a score because of the lack of tumor cells. Seventy-eight percent of the individual discs on the microarray had scores in agreement with those of the whole-section slides. Among biopsy discs with tumor cells present, 94.5% were in agreement with the whole-section slide. The average probability that four randomly chosen biopsy discs, considered together, would accurately identify the presence of p53 staining in a whole section was 0.97 (95% CI.93-1.0).
We conclude that tissue microarrays for squamous cell carcinomas can accurately represent immunohistochemical results of whole-slide specimens when four or more samples are used. Tissue microarrays are an important technique that may be applied to immunohistochemical studies of head and neck cancer.
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES Granular cell tumor of the larynx As a general rule, a pathologist should be wary of making a diagnosis of a laryngeal squamous cell carcinoma in a patient<50 years without ruling out this diagnosis
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS GENERAL
Prognostic factors in squamous cell carcinoma of the larynx.
Eiband JD, Elias EG, Suter CM, Gray WC, Didolkar MS.
Department of Surgery, University of Maryland, Baltimore.
Am J Surg 1989 Oct;158(4):314-7 Abstract quote
One hundred fifty-two patients with squamous cell carcinoma of the larynx were studied. The disease-free survival and overall survival rates were correlated to 12 variables. Seven of them seemed to affect survival.
Poor prognosis was related to (1) advanced stage of disease at diagnosis, (2) cord fixation and massive local invasion, (3) ulceration of the primary tumor, (4) lymph node metastases at diagnosis, (5) glottic lesions had a poorer prognosis than supraglottic ones, (6) locoregional recurrences, and (7) male gender.
However, most of these significant differences were in disease-free survival, and only primary tumor staging; lymph node status; and locoregional recurrences affected overall survival. On the other hand, the other five variables showed no effect on either disease-free or overall survival rates. These included age, race, cell differentiation, type of recurrence, and the initial definitive therapeutic modality.
Development of a new staging system for patients with recurrent laryngeal squamous cell carcinoma.
Lacy PD, Piccirillo JF.
Department of Otolaryngology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Cancer 1998 Sep 1;83(5):910-7 Abstract quote
BACKGROUND: The management of recurrent head and neck squamous cell carcinoma can be challenging to both physician and patient. This is due at least in part to the lack of an accurate and clinically applicable staging system for these patients. The purposes of this study were to examine the survival patterns of patients presenting with recurrent laryngeal tumors, identify key factors affecting prognosis, and combine these factors to create a new staging system to predict survival.
METHODS: The methods included a retrospective chart review of 473 patients with laryngeal squamous cell carcinoma who received their initial treatment at Washington University between 1980 and 1992. From this population, 126 patients (27%) who developed recurrence were identified.
RESULTS: The overall 2-year survival rate was 40% (50 of 124 patients). Four variables affected survival: initial TNM stage, initial treatment, morphologic extent of recurrence, and treatment of recurrence. These variables were entered into a multivariate analysis to determine independent prognostic significance. Three variables were found to be statistically significant: TNM stage (chi-square = 4.6; P = 0.03), initial treatment (chi-square 14.3; P = 0.0002), and extent of recurrence (chi-square = 19.4; P = 0.0001). The process of conjunctive consolidation was used to combine significant variables to create a new staging system for laryngeal recurrence.
CONCLUSIONS: This staging system provides accurate estimates of prognosis, involves no new technology to implement, can aid both the patient and physician in planning treatment, and can be used in observational studies to assess the relative effectiveness of competing therapies.
CD44 Clinicopathologic Significance of Expression of CD44s and CD44v6 Isoforms in Squamous Cell Carcinoma of the Supraglottic Larynx
Juan P. Rodrigo, MD, etal
Am J Clin Pathol 2002;118:67-72 Abstract quote
CD44 splice variants are assumed to have a critical role in the malignant progression of many human tumors. However, the clinical significance of CD44 expression is not yet understood.
The aim of this study was to investigate the prognostic significance of expression of CD44s and CD44v6 isoforms in squamous cell carcinomas of the supraglottic larynx. CD44s and CD44v6 expression was determined by immunohistochemical analysis of paraffin-embedded tissue specimens from 101 patients. There was a significant correlation between decreased CD44s or CD44v6 expression and a poorer histologic differentiation. No relationship was observed with T stage or nodal metastasis. Decreased CD44s expression, but not CD44v6 expression, correlated with increased recurrence rates. There was no correlation between the decreased expression of any isoform tested and survival.
These data confirm a reduction of CD44s and CD44v6 expression in poorly differentiated tumors. However, these changes do not offer a useful adjunct to current prognostic indicators.
Laryngeal carcinoma in females.
Shvero J, Hader T, Feinmesser R, Har-El G, Martin D, Marshak G, Segal K.
Department of Otolaryngology and Head and Neck Surgery, Beilinson Medical Center, Tel Aviv University, Israel.
Eur J Surg Oncol 1996 Feb;22(1):61-4 Abstract quote
Between 1950 and 1992, 96 women with squamous cell carcinoma of the larynx were diagnosed and treated in the Department of Otolaryngology and Oncology at Beilinson Medical Center, Israel, and Long Island College Hospital, Brooklyn, New York.
Fifty-seven female patients (59%) had glottic carcinoma, 72% of them in stage I. Thirty-eight had supraglottic carcinoma, 68% of them in stages II and III. One patient had stage I subglottic carcinoma. Treatment varied between radiotherapy, surgery, or combined surgery with radiation and/or chemotherapy. The 5-year survival rate was 87%. Although most of the patients had glottic carcinoma in stage I, there was also a high percentage with supraglottic carcinoma, most in advanced stages and with metastases to other regions.
The prognosis is not different from that in men. Smoking is an important factor in glottic carcinoma, but not as important as in males.
Distant metastases in laryngeal squamous cell carcinoma.
Yucel OT, Yilmaz T, Unal OF, Turan E.
Dept. of Otorhinolaryngology and Head and Neck Surgery, Hacettepe University, Ankara, Turkey.
J Exp Clin Cancer Res 1999 Sep;18(3):285-8 Abstract quote
Distant metastases (DM) is the point of concern and seems to be on the rise with the improved control of the laryngeal cancer in the primary site and neck regions. Prognostic factors must be evaluated to improve the detection of DM at early stage of the disease.
Therefore, we have analyzed our cases of laryngeal squamous cell carcinoma with DM to find out the risk factors in these patients. We analyzed the records of laryngeal squamous cell carcinoma patients with DM. The records were evaluated according to distant metastases site, TNM staging, the metastases at the neck, treatment and survival.
The incidence of DM was 7.2% in our series. Lung is the most common site of DM in laryngeal squamous cell carcinoma. Staging grouping has been helpful in predicting DM, most of the cases were in stage III and IV (85%). Supraglottic lesions is the most common site in patients with DM. The recurrence in the locoregional site was observed in 47% of cases.
The overall survival with DM is 28 months, without DM 22 months. The patients with DM in laryngeal squamous cell carcinoma were from the group with supraglottic lesions, stage 3, 4a and 4b. Stage grouping seems to be a better indicator of DM rather than T or N stage alone. The most common site of metastasis is the lung.
TREATMENT COMBINED MODALITIES
Advanced carcinoma of the larynx: results of surgery and radiotherapy without induction chemotherapy (1980-1985): a multivariate analysis.
Nguyen TD, Malissard L, Theobald S, Eschwege F, Panis X, Bachaud JM, Rambert P, Chaplain G, Quint R.
Institut Jean-Godinot, Reims, France.
Int J Radiat Oncol Biol Phys 1996 Dec 1;36(5):1013-8 Abstract quote
PURPOSE: Induction chemotherapy has been proposed in the case of advanced laryngeal cancer in order to preserve laryngeal function in those patients who are complete responders. To clarify the treatment policies, a retrospective multicentric analysis of 116 patients with advanced carcinoma of the larynx treated by radical surgery and postoperative radiotherapy was carried out in order to evaluate prognostic factors for local control and survival.
METHODS AND MATERIALS: Between 1980 and 1985, 116 patients with Stage III squamous cell carcinoma of the larynx underwent radical surgery and postoperative radiotherapy with a curative intent. Treatments were very homogenous, and doses delivered were in the range of 50-65 Gy according to nodal involvement and surgical margins status.
RESULTS: The local recurrence rate and the local disease-free survival rate at 5 years were 22.5% and 76.3%, respectively. Actuarial survival at 5 years was 68.3% with 44 patients still alive with no evidence of disease (NED) with more than 5 years follow-up. For both overall survival and relapse-free survival, cervical node involvement with capsular rupture was found to be the only significant adverse pronostic factor in univariate and multivariate analysis. No other parameter was predictive either for local recurrence or for survival.
CONCLUSIONS: Local prognosis and survival depend largely on nodal involvement and capsular rupture while increasing doses of radiation strategy is likely to reduce the risk of local and nodal recurrence. Preservation of functional larynx is certainly an important goal to achieve when treating advanced carcinoma of the larynx, provided that local failure rate and survival be similar. In the unique randomized study previously published in the literature comparing radical surgery and postoperative radiotherapy to induction chemotherapy and radiotherapy, the local-regional failure rate was drastically increased in the chemotherapy arm. Other results from well-designed controlled studies are awaited before recommending systematic induction chemotherapy and larynx preservation in complete responders. On the other hand, testing synchronous or alternated chemotherapy vs. induction chemotherapy may address the pending questions about the optimal treatment of advanced laryngeal carcinoma.
Concurrent chemotherapy and radiotherapy as initial treatment for stage II supraglottic squamous cell carcinoma.
Nagahashi T, Fukuda S, Homma A, Yagi K, Furuta Y, Inuyama Y.
Department of Otolaryngology, Hokkaido University School of Medicine, Sapporo, Japan.
Auris Nasus Larynx 2001 May;28 Suppl:S95-8 Abstract quote
OBJECTIVE: To evaluate the efficacy and safety of concurrent carboplatin (CBDCA) and radiotherapy for laryngeal carcinoma. we investigated survival rates and laryngeal preservation rates in patients with this treatment modality and those with radiation therapy only.
METHODS: We underwent chemotherapy with CBDCA and conventional radiotherapy concurrently to 17 patients with untreated stage II (T2NOM0) supraglottic squamous cell carcinoma since November 1990. CBDCA (100 mg/m2) was administered intravenously once a week concurrently with radiotherapy (2.5 Gy/fr, 4 times a week). At the dose of 40 Gy, the results were evaluated, and some of the patients underwent planned surgery and others continued the radiotherapy up to 65 Gy.
RESULTS: Overall 5-year survival rate by Kaplan-Meier method was 81.1%. Actual laryngeal preservation rate was 76.0%. Toxicity over grade III was noticed in two patients. Compared with 14 cases of historical controls, which were treated by radiation therapy alone between 1988 and 1990, the cases with concurrent radiotherapy and chemotherapy had statistically significant advantage in overall successful laryngeal preservation rate (P < 0.05), whereas the two groups were not significantly different in the overall 5-year survival rate.
Treatment of early stage squamous-cell carcinoma of the glottic larynx: endoscopic surgery or cricohyoidoepiglottopexy versus radiotherapy.
Bron LP, Soldati D, Zouhair A, Ozsahin M, Brossard E, Monnier P, Pasche P.
Department of ENT and Head and Neck Surgery, the Centre Hospitalier Universitaire Vaudois, av Bugnon 46, CH-1011, Lausanne, Switzerland.
Head Neck 2001 Oct;23(10):823-9 Abstract quote
BACKGROUND: Both surgery and radiotherapy are recognized treatments of T1-T2 squamous cell carcinoma of the larynx. We retrospectively analyze and compare the oncological outcome of patients treated in a single institution, either by endoscopic surgery or partial supracricoid laryngectomy versus radiation therapy.
METHODS: The medical records of 156 patients treated between 1983 and 1996 with either surgery (n = 75) or radiotherapy (n = 81) were reviewed. Male to female ratio, median age, and T-stage distribution were comparable.
RESULTS: With a median follow-up time of 59 months, the 5-year cause-specific survival rate of 93% was identical for both groups. The actuarial incidence of metachronous second primaries was 7% at 5 years. Local control at 5 years remained 84% after surgery and 77% after radiotherapy. Anterior commissure infiltration was shown to represent a negative predictive factor of local control for radiotherapy (p =.01). Salvage treatment brought ultimate local control to 96% of patients after surgery and 94% after radiation therapy with long-term laryngeal preservation rate altered significantly (p =.05) in the group of patients who received radiotherapy (90.1% vs 97.4%).
CONCLUSION: The treatment of laryngeal cancer is always a compromise between oncological efficiency and preservation of function. Our data suggest that, assuming proper selection of patients, radiation therapy and surgery yield similar local control and survival rates. The functional disadvantages after surgery are moderate and clearly counterbalanced by a significant decrease in long-term laryngeal preservation rate after radiotherapeutic treatment.
Treatment results and prognostic factors of advanced T3--4 laryngeal carcinoma: the University of California, San Francisco (UCSF) and Stanford University Hospital (SUH) experience.
Nguyen-Tan PF, Le QT, Quivey JM, Singer M, Terris DJ, Goffinet DR, Fu KK
Department of Radiation Oncology, University of California, San Francisco, CA, USA.
Int J Radiat Oncol Biol Phys 2001 Aug 1;50(5):1172-80 Abstract quote
PURPOSE: To review the UCSF-SUH experience in the treatment of advanced T3--4 laryngeal carcinoma and to evaluate the different factors affecting locoregional control and survival.
METHODS AND MATERIALS: We reviewed the records of 223 patients treated for T3--4 squamous cell carcinoma of the larynx between October 1, 1957, and December 1, 1999. There were 187 men and 36 women, with a median age of 60 years (range, 28--85 years). The primary site was glottic in 122 and supraglottic in 101 patients. We retrospectively staged the patients according to the 1997 AJCC staging system. One hundred and twenty-seven patients had T3 lesions, and 96 had T4 lesions; 132 had N0, 29 had N1, 45 had N2, and 17 had N3 disease. The overall stage was III in 93 and IV in 130 patients. Seventy-nine patients had cartilage involvement, and 144 did not. Surgery was the primary treatment modality in 161 patients, of which 134 had postoperative radiotherapy (RT), 11 had preoperative RT, 7 had surgery followed by RT and chemotherapy (CT), and 9 had surgery alone. Forty-one patients had RT alone, and 21 had CT with RT. Locoregional control (LRC) and overall survival (OS) were estimated using the Kaplan--Meier method. Log-rank statistics were employed to identify significant prognostic factors for OS and LRC.
RESULTS: The median follow-up was 41 months (range, 2--367 months) for all patients and 78 months (range, 6--332 months) for alive patients. The LRC rate was 69% at 5 years and 68% at 10 years. Eighty-four patients relapsed, of which 53 were locoregional failures. Significant prognostic factors for LRC on univariate analysis were primary site, N stage, overall stage, the lowest hemoglobin (Hgb) level during RT, and treatment modality. Favorable prognostic factors for LRC on multivariate analysis were lower N stage and primary surgery. The overall survival rate was 48% at 5 years and 34% at 10 years. Significant prognostic factors for OS on univariate analysis were: primary site, age, overall stage, T stage, N stage, lowest Hgb level during RT, and treatment modality. Favorable prognostic factors for OS on multivariate analysis were lower N stage and higher Hgb level during RT.
CONCLUSION: Lower N-stage was a favorable prognostic factor for LRC and OS. Hgb levels > or = 12.5 g/dL during RT was a favorable prognostic factor for OS. Surgery was a favorable prognostic factor for LRC but did not impact on OS. Correcting the Hbg level before and during treatment should be investigated in future clinical trials as a way of improving therapeutic outcome in patients with advanced laryngeal carcinomas.
End results of a prospective trial on elective lateral neck dissection vs type III modified radical neck dissection in the management of supraglottic and transglottic carcinomas.
Brazilian Head and Neck Cancer Study Group. Head and Neck Surgery Department, Hospital A. C. Camargo, Rua Professor Antonio Prudente, 211, 01509-010 - Sao Paulo, Brazil.
Head Neck 1999 Dec;21(8):694-702 Abstract quote
BACKGROUND: Either modified type III radical neck dissection (MRND) or lateral neck dissections (LNDs) are considered valid treatments for patients with laryngeal carcinoma with clinically negative neck findings (N0). The object of this prospective study was to compare complications, neck recurrences, and survival results of elective MRND and LND on the management of laryngeal cancer patients. Patients and Methods This prospective randomized study began in 1990, and patient accrual was closed on December 1993. A total of 132 patients was included in the trial. All patients had previously untreated T2-T4 N0 M0 supraglottic or transglottic squamous cell carcinoma. No significant imbalance was found between groups with respect to demographic, clinical, pathologic, and other therapeutic variables. Seventy-one patients were given MRNDs (13 bilateral) and 61 were given LNDs (18 bilateral).
RESULTS: The false-negative rate was 26%, and most positive nodes were sited at levels II and III. Complications and period of hospitalization were similar in both groups. There were 6 ipsilateral neck recurrences (4 in the MRND group, and 2 in the LND group). The 5-year actuarial survival calculated by Kaplan-Meier method was 72.3% in the MRND group and 62. 4% in the LND group (log-rank test p =.312).
CONCLUSIONS: The rate of false-negative nodes in supraglottic and transglottic carcinomas was 26%, and most positive nodes were at levels II and III. The rates of 5-year overall survival, neck recurrences, and complications were similar in both groups. These results confirm the efficacy of lateral neck dissection in the elective treatment of the neck in patients with supraglottic and transglottic carcinomas.
Radiation treatment of glottic squamous cell carcinoma, stage I and II: analysis of factors affecting prognosis.
Franchin G, Minatel E, Gobitti C, Talamini R, Sartor G, Caruso G, Grando G, Politi D, Gigante M, Toffoli G, Trovo MG, Barzan L.
Department of Radiotherapy, Centro di Riferimento Oncologico, Aviano, Italy.
Int J Radiat Oncol Biol Phys 1998 Feb 1;40(3):541-8 Abstract quote
PURPOSE: At least in some European Countries, there is still considerable controversy regarding the choice between surgery and radiotherapy for the treatment of patients with early laryngeal-glottic carcinoma.
METHODS AND MATERIALS: Two hundred and forty-six patients with laryngeal-glottic neoplasms, Stage I-II, were treated with radical radiotherapy. Before radiotherapy the patients were evaluated to determine the surgical procedure of choice. Either 66-68.4 Gy (33-38 fractions) or 63-65 Gy (28-29 fractions) of radiation therapy (RT) were administered. The overall disease free survival was determined for each subgroup of patients. Univariate and multivariate analyses were performed to determine significant prognostic variables.
RESULTS: Five- and 10-year overall survival rates were 83 and 72%, respectively. At a median follow-up of 6 years 204 patients are alive and disease free. No patient developed distant metastases. One patient died of a large local recurrence, 38 patients died of causes unrelated to their tumor, and 3 patients were lost to follow-up. The multivariate analysis confirmed that performance status (PS), macroscopic presentation of the lesion, and persistence of dysphonia after radiotherapy are significant prognostic factors.
CONCLUSIONS: According to the multivariate analysis, the patients with PS > 80 and with exophytic lesions are eligible for radical RT. The surgical procedure proposed for each patient was not found to be an independent prognostic factor.
Adjuvant radiotherapy influences the survival of patients with squamous carcinoma of the head and neck who have poor prognoses.
De Stefani A, Magnano M, Cavalot A, Usai A, Lerda W, Mola P, Albera R, Ragona R, Gabriele P, Bussi M, Cortesina G.
Department of Clinical Physiopathology, Second ENT Clinic, Mauriziano Hospital "Umberto I", Turin, Italy.
Otolaryngol Head Neck Surg 2000 Nov;123(5):630-6 Abstract quote
The treatment of carcinoma of the head and neck in recent years has improved significantly, chiefly thanks to progress in surgery and radiotherapy. Despite these advances, the survival statistics reported in the literature show no appreciable evidence of radical improvement.
The aims of this study were to evaluate the impact on survival achieved with the combination of surgical and postoperative radiotherapy in patients with advanced head and neck carcinomas and to identify the prognostic value of several host- and tumor-related factors that can influence the results of combined treatment. We retrospectively reviewed the medical records of 394 patients with stage III and IV carcinoma of the head and neck, of whom 170 (43%) underwent surgery alone and 224 (57%) received combined surgery and postoperative radiotherapy. The 394 patients were stratified for a set of variables including the patient's condition, the characteristics of the tumor, and the modality of treatment. Univariate analysis revealed that coexistent medical diseases, the size and site of the primary lesion, the stage of the tumor, and certain pathologic features had a negative impact on survival. Multivariate analysis showed that the removal of lymph nodes and postoperative radiotherapy can have a positive influence and can improve the prognosis.
We compared the survival rates of the patients treated with surgery alone with those of the patients who underwent combined treatment, and we observed that the two survival curves were comparable, even if there was a bias because the combined treatment group consisted of patients with negative prognostic factors. The meaning of these results, compared with data from the literature, has been discussed.
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Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
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