Squamous Cell Metaplasia Research Articles

Clinicopathological studies of minimal thyroid and ordinary thyroid cancers.

Clinicopathological studies were carried out on 27 patients with minimal thyroid cancer and 56 with ordinary thyroid cancer at Kanazawa University, from April, 1979 to December, 1982. There was a significant difference in the rate of preoperative diagnosis between the minimal and the ordinary cancer groups. Subtotal thyroidectomy with modified neck dissection was usually performed in both groups. The histological types in minimal cancer group included 16 papillary carcinomas, 7 nonencapsulated sclerosing carcinomas, one follicular carcinoma, one anaplastic carcinoma with squamous cell metaplasia and two multiple mixed carcinomas. There was no significant difference in the rates of intrathyroidal and lymph node metastases between the two groups. While the metastatic lesions of sclerosing carcinoma were localized to the central cervical lymph nodes, the ordinary cancer in general and the papillary variant of minimal cancer metastasized not only to the central cervical lymph nodes but also to the ipsilateral and even to the contralateral jugular lymph nodes.

A 26-week inhalation toxicity study with formaldehyde in the monkey, rat, and hamster

This inhalation study involved simultaneous exposure of five groups of 6 male Cynomolgus monkeys, 20 male and 20 female Fischer 344 rats, and 10 male and 10 female Syrian golden hamsters for 22 hr per day, 7 days per week for 26 weeks to formaldehyde gas. The cumulative mean exposure concentrations were 0, 0, 0.19, 0.98, and 2.95 ppm for the two control groups, low-, mid-, and high-level exposure groups, respectively. There was no treatment-related mortality during the study. In monkeys, the most significant findings were hoarseness and congestion and squamous cell metaplasia in the nasal turbinates of the 2.95-ppm exposure group. There were no signs of toxicity in the lower-level exposure groups. In the rat, the only observations of possible responses to exposure were found in the 2.95-ppm exposure group. These findings consisted of squamous metaplasia in the nasal turbinates, decreased body weights starting during the second week of the study, and decreased liver weights. In contrast to monkeys and rats, hamsters did not show any significant responses to exposure even at 2.95 ppm. It was concluded that nearly continuous exposure of monkeys and rats for six months at a level of 2.95 ppm of formaldehyde clearly elicited an effect while exposures below this level did not appear to demonstrate an effect. It further appeared that the monkey and rat were more sensitive to formaldehyde exposure than the hamster.

Benzo(a)pyrene-induced early cytopathologic changes and peroxidase activity in the endometrium of ovariectomized rats

The present study was designed to investigate whether benzo(a)pyrene (BP) alone would have cytopathologic effects on the endometrium of ovariectomized rats, and whether DES can modulate or facilitate this cytopathology. The morphology and cytochemically detectable peroxidase activity in the endometrial epithelium of castrated rats were studied 24 hr after sc administration of three to six doses on consecutive days (one dose per day) either of corn oil, BP (50 mg/kg/day), DES (20 μg/kg/day), or a combination of the latter two agents. BP alone induced mitosis, peroxidase activity, and focal squamous cell metaplasia in the endometrial epithelium of castrated rats. Peroxidase activity was weak in the granular endoplasmic reticulum of the normal epithelial cells after three and six doses of BP. However, in the focal metaplasia, the superficial squamous cells contained strong peroxidase activity after six consecutive daily doses of BP. The focal metaplasia present only after six doses of BP consisted of three to four layers of squamous cells and one to two layers of basal cells. DES-treated animals showed no formation of metaplasia or structural alterations in the epithelium, but intense peroxidase activity was present in epithelial cells after three or six daily doses. The castrates treated with three or six combined doses of BP and DES showed significant ultrastructural changes in the epithelial cells. Vacuolization of the cisternae of the granular endoplasmic reticulum was observed in the epithelial cells after three doses of BP-DES. Distinct dilation and degranulation of the granular endoplasmic reticulum as well as enlargement of mitochondria were found in all the epithelial cells of the pseudostratified hyperplastic epithelium after six consecutive daily doses of the combination, BP-DES. These ultrastructural aberrations are clearly indicative of a cytotoxic effect of BP on the endometrial epithelial cells. Collectively these findings suggest that sc administration of BP induces peroxidase activity which may lead indirectly to lesions in the endometrium of ovariectomized rats, and DES may enhance the cytotoxicity of BP by a similar mechanism.

Hyperplastic, preneoplastic and neoplastic lesions found in 83 human pancreases.

A thorough histologic examination of the pancreas was performed on autopsy material from 83 military veterans aged 35-88 years. Hyperplastic, preneoplastic and neoplastic alterations were recorded by severity, multiplicity, location and age. From this material, two patients had clinically known primary, and three had secondary (metastatic), pancreatic cancer. The following occult malignant lesions were found: two early cancers (one adenocarcinoma and one adenosquamous cell carcinoma), one ductal carcinoma in situ and seven ductular carcinomas in situ. Among patients with ductular carcinoma in situ, three had pancreatic caner and the remaining four had cancers of other sites (ethmoid, ear, colon, prostate). One patient who was clinically diagnosed as having lung cancer with selective metastases to the pancreas was found to have pancreatic adenosquamous cell carcinoma with lung metastases. Hence, the incidence of neoplastic exocrine lesions was around 10%. In addition, hyperplasia of the ductal and ductular epithelium (in 57% and 39% of the patients, respectively), squamous cell metaplasia of the ductules (in 48% of the cases), as well as endocrine tumors (islet cell adenoma, 10%; mixed ductular-insular adenoma, 3%) were found. Most lesions occurred in the pancreatic head, a few in the tail. These data and other reports led to the conclusion that, first, the overall incidence of pancreatic cancer appears to be higher than previously reported. Malignant lesions seem to remain clinically occult, either because patients die of other diseases or because of the significantly long latency between premalignant lesions and clinically recognizable invasive cancer. Second, the ductular cells appear to be the progenitor cells of a variety of tumor types, including squamous cell cancer and islet cell tumors, as in the authors' experimental model.

Results of lung cancer screening programs in Japan.

In 1953 we began in Japan a lung cancer detection program by chest X-ray surveys amongst several groups including employees of the Tokyo Metropolitan Government (TMG). The results obtained from this 27-year survey indicate that chest X-rays are effective in the detection of early stage lung cancer located peripherally but not centrally in the lung. At the Department of Surgery, Tokyo Medical College, 54 cases of early stage lung cancer were treated; 45 cases were peripheral and only nine cases were central. Of the nine centrally located tumors only two (22%) were detected by chest X-ray survey, as opposed to 71% of the peripheral-type cases similarly detected. Sputum cytology surveys have thus gained increasing attention in Japan for the detection of early stage central lung cancer, particularly in cases where the chest X-ray is negative. A sputum cytology study is thus being conducted amongst high risk employees of the TMG as well as amongst local residents of the Itabashi area in Tokyo aged 40 years and over, but the results are as yet inconclusive. However, in addition to detecting early stage lung cancer, the objective of sputum cytology surveys should include the detection of atypical squamous cell metaplasia, since this condition has been shown experimentally [Kato et al., this Symposium] and clinically [1, 17, 18, 21] to be involved in the development of squamous cell carcinoma. Squamous cell metaplasia is therefore checked for in our survey cases, and chronological changes of nuclear atypia are monitored. Our chest X-ray survey of employees of the TMG is a representative study that has been carried out over a long period of time. There are several other groups conducting sputum cytology and/or chest X-ray surveys in Japan, particularly the National Kinki Central Hospital Group, where two of us (K.S. and K.F.) have initiated a chest X-ray and sputum cytology project which has yielded a high rate of lung cancer detection.

Recovery of bronchial epithelium on stopping smoking.

Bronchial biopsy specimens were studied from 19 patients, comprising five non-smokers, eight current smokers, and six people who had given up smoking between two and 16 years previously. By using a recently developed morphometric technique the structural state of the bronchial epithelium was assessed and described by a score, which specifies the extent to which the epithelial histology departs from the normal, through the changes of mucous-cell hyperplasia and squamous-cell metaplasia. The epithelium was nearer normal in former smokers than current smokers in each of six pairs matched for smoking history. The numerical scale permitted statistical analysis with a precision that is not possible with data based on subjective diagnosis alone: the results of comparing histology with pack-years of cigarette consumption were consistent with the hypothesis that structural recovery occurs in bronchial epithelium in people who stop smoking for over two years.

Histologic subclassification of the cystadenolymphoma of the parotid gland. Analysis of 275 cases.

Cystadenolymphomas (CAL) of the parotid gland are variable in their epithelial differentiation and the ratio of the epithelial tumor component to lymphoid stroma. Two hundred and seventy five cases of CAL from the files of the Salivary Glands Register of the Institute of Pathology, University of Hamburg (1965-1979) were analysed. Their pathogenesis from parenchyma included in regional lymph nodes is discussed. The following subclassification was established. 1. Depending on to the ratio of epithelial tumor component to lymphoid stroma, three subtypes were distinguished. Subtype 1, "typical CAL" with an epithelial tumor component of 50%, amounted to 77% of all cases of CAL studied. Oncocytic differentiation and focal metaplasia to goblet cells or squamous epithelium was also found. 13.5% of CAL were classified as subtype 2, "stroma-poor CAL" with an epithelial tumor component of 70 to 80%. The tumor structure was similar to that of an oncocytoma in places. Two per cent of the CAL were in subtype 3, "stroma-rich CAL" with an epithelial tumor component of only 20 to 30%. Subtype 3 was found solely in men. The average age at presentation (61 years) was slightly lower than that of all the cases studied (65 years). 2. In 7.5% of the cases large areas of squamous cell metaplasia and regressive changes was found within a CAL. These cases were classified as subtype 4 ("metaplastic CAL"). The average age was 67 years. The case histories showed that 20% of these metaplastic CAL had previously been irradiated. 3. Bilateral CAL was found in 7.5% of the cases. In 4% multifocal CAL occurred in the parotid gland unilaterally. Recurrences were observed in 2% of all CAL. 4. Carcinoma in CAL is rare (we found two cases in our own material). In 50% of all cases reported radiotherapy was mentioned in the case histories. 5. Malignant tumors coincident with CAL were recorded in 3% of the cases. 6. The lymphoid stroma showed reaction patterns similar to those of the regional lymph nodes. These included granulomatous changes (foreign body granuloma with cholesterol deposits, tuberculosis) and tumor metastases. In the neighborhood of oncocytic tumor epithelium focal accumulations plasma cells forming IgA and IgG were found. Metaplasia to squamous epithelium is believed to be caused by circulatory disturbances, irradiation, and other noxae. In the differential diagnosis of the stroma-poor subtype 2, oncocytoma and cystic sialadenoma must be excluded, and in the differential diagnosis of subtype 4 (the metaplastic CAL), sebaceous adenoma, mucepidermoid tumor, squamous cell carcinoma, lymphoepithelioma, and other non-tumorous lesions of the parotid gland (lymphoepithelial cysts, myoepithelial parotitis) must be ruled out. Our findings suggest that CAL develops from parenchyma included in parotid lymph nodes with the oncocytic ductal epithelium representing the neoplastic component.

ARGYROPHIL CELLS IN THE EXOCRINE PANCREAS

The silver positive cells of the exocrine pancreas and primary pancreatic cancers were studied with the Grimelius silver stain and the Fontana-Masson technique. In the pancreas, cells containing black granules with the Grimelius method, which at the same time react negative to Fontana-Masson, are considered argyrophil. These cells were present in the basal portion of some of the acinar tissue and in the ductal epithelia, as well as in the A cells of islets. The incidence and distribution of these argyrophil cells were also studied in a variety of ductal lesions. In the so-called ductal proliferation numerous numbers of positive cells were found. Argyrophil cells were frequently situated in the basal portion of ductal squamous cell metaplasia. In goblet cell metaplasia the numbers were few, and less than in normal ducts. We concluded that the distribution and incidence of argyrophil cells in the ductal epithelia is related to chronic pancreatitis, and in particular to regenerative processes. The incidence of argyrophil cells in primary pancreatic cancer, excluding islets cell origin, was 18 per 41 cases (43.4%). We considered them pancreatic cancer with argyrophil cells.

Minor salivary gland calculi: A clinicopathologic study of forty-seven new cases

An analysis of forty-seven previously unreported cases of minor salivary gland calculi revealed that they were usually solitary, firm, freely movable, small masses. Also, we noted that these calculi exhibited a striking predilection for the upper lip and buccal mucosa of adults. The organic matrix of all calculi was similar; however, the amount of mineralized material was variable. A variety of types of epithelial metaplasia was noted in the pericalcular ducts, with the most common type being squamous-cell metaplasia. Chronic periductal and lobular inflammation in addition to duct ectasia were common findings. The cause of minor salivary gland calculi is not known; however, local factors, such as duct morphology or biochemical alterations, or both, may be involved.

A method for experimental induction of bronchogenic carcinoma in subcutaneously implanted bronchial autograft in dogs

A method for induction of carcinoma in subcutaneously implanted bronchial autografts in dogs is described. Four to 6 weeks after successful bronchial autografting, 30 to 90 mg. amounts of 3-MC or B(a)P suspended in sterile saline solution containing 1 percent CMC was injected into the lumen of the graft. The mucosal changes were followed histologically by excision of biopsy specimens and cytologically by needle aspiration biopsies. Three dogs developed squamous cell carcinomas invading deep into the submucosal area as early as 13 to 30 weeks after the first carcinogen treatment. The remaining eight experimental dogs showed various grades of squamous cell metaplasia with atypia within 30 weeks. Subsequently examined specimens revealed atypical metaplastic and proliferative changes further advanced than those seen in the initial biopsy specimens. The advantages of this method for a better understanding of the development of bronchogenic carcinomas are discussed.

Partial replacement of urinary bladder by autologous gallbladder

In an effort to find a more suitable method of partial urinary bladder replacement for those patients with either a damaged or contracted bladder, the use of the autologous gallbladder was studied. The urinary bladders of 6 female dogs were partially resected, and the defective portions were replaced by autologous gallbladder transplants. After six weeks, the gallbladder mucosa showed evidence of squamous cell metaplasia progressing toward transitional cell epithelium with minimal necrosis. The muscular layer showed extensive granulation tissue and revascularization. No changes were detected in the upper urinary tracts. No mortality or detectable morbidity was associated with the procedure. It appears that the gallbladder may have a role to play in partial urinary bladder replacement.

Bleomycin lung (author's transl)

Histological and electron-microscopic study of the lungs of 15 patients who had been treated with bleomycin for advanced squamous cell carcinoma demonstrated marked histological changes in nine. They were typical of bleomycin effects: alveolitis, intra-alveolar and interstitial oedema, pulmonary hyaline membranes, disseminated intravascular coagulation, intraalveolar and interstitial fibrosis, atelectasis, metaplasia and dysplasia of the alveolar lining cells. These lesions had a focal distribution, preferentially in the subpleural and periseptal regions. Each of these lesions alone is a non-characteristic reaction, but their combination makes it a distinct entity (bleomycin lung). Three different clinical courses were noted: (1) cases with no or little abnormality; (2) acute form during or shortly after bleomycin treatment; (3) chronic, progressive form of bleomycin lung which may end fatally as late as 1 1/2 years after bleomycin treatment had been discontinued. Squamous cell metaplasia is the most characteristic sign of bleomycin lung. It should not be confused with pulmonary metastases. To prove the diagnosis of bleomycin lung often requires systematic histological investigation. A schema of the pathogenesis of the bleomycin lung is proposed in which the formation of microthrombi plays an important part.

Early indices of cancer risk among uranium miners with reference to modifying factors.

Cancer of the lung develops from normal epithelial changes that progress from regular squamous cell metaplasia to progressively more and more atypical stages to eventually develop into squamous-cell carinoma in situ. The in situ stage sheds large numbers of cells that can often be identified as malignant cells in sputum. This allows early diagnosis, localization, and resection, increasing, it is hoped, survival from bronchogenic carcinoma.

Cancer induction in subcutaneously implanted bronchial autograft of a dog by 3-methylcholanthrene.

An experimental cancer induction in subcutaneously autoimplanted bronchial grafts in dogs was studied. After successful bronchial autografting, 3-methylcholanthrene or 3,4-benzo[a]pyrene suspended in sterile saline solution containing 1% carboxymethylcellulose was injected into the lumen. Twenty-eight weeks after this treatment, an invasive squamous cell carcinoma with concomitantly existing atypical squamous metaplasia was found in one dog by histological examination. Squamous cell metaplasia was also observed in two other dogs at 24th experimental week. Cytological examination revealed the findings corresponding to these epithelial changes. Remaining 15 dogs are still living and under observation.

Picibanil (溶連菌製剤) の近交系ACI/Nラット移植膀胱腫瘍に対する免疫反応について

Transitional cell carcinomas (BC-47, BC-35 and BC-50) were produced in urinary bladder of ACI/N rats by oral administration of N-butyl-N-butanol (4) nitrosamine (BBN). The cells of these carcinomas can multiply successively in vitro and these cultured cells are always iso-transplantable into the urinary bladder of ACI/N rats. BC-47 is a high antigenic transitional cell carcinoma accompanied with squamous cell metaplasia, BC-35 is a moderate antigenic and BC-50 is a low antigenic. PICIBANIL is a biological preparation obtained from a low virulent mutant of lancefield's type III, group A Streptococcus pyogenes. PICIBANIL attacks directly the tumor cells and also potenciates the defence mechanism of the host.In vitro study.Effects of PICIBANIL and Mitomycin C (MMC) for BC-47 cells were tested in cell culture by the method of colony inhibition assay. Complete inhibition of cell growth was seen in PICIBANIL at a concentration of 1000μg/3ml. No inhibition was seen at a concentration of 200μg/3ml and below. This concentration was higher than the concentration of PICIBANIL in the bladder wall of rats, when 0.5mg of the agent was injected intraperitoneally. Complete inhibition of BC-47 cells was seen in MMC at a concentration of 10μg/3ml, and no inhibition was seen at a concentration of 0.01μg/3 ml and below.In vivo study.Ten days after implantation of various cancer cells (2×108) into the urinary bladder of ACI/N rats, when the growth of carcinomas was confirmed macroscopically, the first injection was done as follows. In case of BC-47, BC-35 and BC-50, 0.5mg of PICIBANIL alone and in case of BC-47, 0.5mg of PICIBANIL combined with 1.0mg of β-methasone and 0.1mg of MMC were injected intraperitoneally. These injections were repeated 5 times at one day interval.Complete regression of all high antigenic BC-47 carcinomas were seen with PICIBANIL therapy alone, but this effect of PICIBANIL was cancelled by combination of β-methasone due to the immunosuppressive effect of this steroid.The effect of MMC for BC-47 was a strong inhibition of tumor growth of the bladder wall, but no complete regression was seen. Histologically, a remarkable lymphocytic infiltration and appearance of foreign body giant cells phogocytizing horny materials were seen in the bladder carcinoma from BC-47, treated with PICIBANIL. And then tumor cells disappeared completely.However, such immunologic reactions were not seen in the same carcinoma when it was treated with PICIBANIL combined with β-methasone. Similarly, BC-35 and BC-50 did not show immunologic reactions even if they were treated with PICIBANIL alone. In BC-47 carcinomas treated with MMC, destroyed tumor cell were observed in histologically.It was thus supposed that the mechanism of the therapeutic effect of PICIBANIL was an acceleration immunologic reaction of the system. On the contrary, that of MMC was a direct destruction of tumor cells.

HISTOLOGICAL CHANGES IN THE SUBMANDIBULAR GLANDS OF RATS AFTER INTRADUCTAL INJECTION OF CHEMICAL CARCINOGENS

Carcinogens injected into the excretory canal of submandibular gland of Donryu rats revealed the following histologic changes in salivary glands. 20-Methylcholanthrene induced squamous cell metaplasia, fibrosis in the early stages, and "benign lymphoepithelial lesion"-like pattern after 3 months. Dense hyalinization occurred after 4-5 months with so-called "mixed tumor"-like pattern. In the later stages epidermoid carcinoma and fibrosarcoma were observed. 9, 10-Dimethylbenzanthracene caused degenerative change, metaplasia, fibrosis and cell infiltration, and later carcinoma and sarcoma appeared at a high rate. 4-Nitroquinoline-N-oxide led to dense hyalinization and so-called "mixed tumor"-like pattern was observed in many specimens. N-nitroso-N-methyl urethane and N-methyl-N-nitroso-N'-nitroguanidine revealed metaplastic changes, fibrosis and lymphoid infiltration. Scarlet red induced remarkable infiltration and aggregation of lymphoid cells, showing benign "lymphoepithelial lesion"-like pattern.

Carcinoma of the Urinary Bladder

CARCINOMA of the urinary bladder is primarily a disease of the elderly, with a peak incidence among those 60 to 70 years old. Each year approximately 9,000 persons in the United States die of urinary bladder cancer, the incidence being three times as frequent in men as in women. The cause of the vast majority of urinary bladder tumors has not been determined. Nevertheless, several causative agents (such as 2-naphthalamine, xenylamine, 4-nitrobiphenyl, benzidine, phenacetin, and caffeine) have been identified as carcinogens, and an increased incidence of bladder carcinoma is reported in workers in the rubber, printing, and leather industries.¹ Most bladder carcinomas are transitional cell tumors of varying degrees of differentiation. Squamous cell metaplasia is seen in many transitional cell carcinomas, particularly the less well-differentiated ones. However, except when schistosomiasis is the cause, true squamous cell carcinomas are rare. Adenocarcinomas also are uncommon. On initial examination, the commonest sign

Development of carcinoma of the lung as reflected in exfoliated cells.

Cytologic examinations of sputum collected periodically since 1957 on a group of uranium miners have been studied and related to the development of bronchogenic carcinoma. Many individuals developed abnormal squamous cell metaplasia that gradually progressed, in several, to develop invasive carcinoma. This progression has been classified into mild, moderate, and marked atypical, squamous cell metaplasias and carcinoma in situ. Cigarette smoking and uranium mining were both associated with the prevalence of these atypias, and with carcinoma in situ and invasive cancer. Neither of these agents, however, appeared to be strongly associated with the duration of the stages of atypia. Age at start of uranium mining was more strongly associated with age at development of carcinoma in situ than other factors tested. There appears to be an average period of 4 or 5 years during which individuals exfoliate cells that are markedly atypical or represent carcinoma in situ in their sputum before developing invasive carcinoma of epidermoid or small cell, undifferentiated varieties. Periodic sputum surveillance of groups at elevated risk of bronchogenic cancer can utilize this period for early detection and treatment.

Transplantability of urinary bladder carcinomas induced in ACI-N rats by oral administration of N-butyl-N-butanol(4)-nitrosamine and its acetate

Carcinogenic effect of N-butyl-N-butanol (4) nitrosamine (BBN) and its acetate (BBN-Ac) was studied in ACI/N rats. The possibility of iso-transplantation of the cancer thus formed was also studied.Fifty-seven male rats were divided into 5 groups as follows;Group A: 20ml of 0.01% BBN was given daily for 25 weeks.Group B: 4ml of 0.05% BBN daily and 20ml of water twice a week for 25 weeks.Group C: 20ml of 0.05% BBN daily for 25 weeks.Group D: 20ml of 0.06% BBN-Ac daily for 25 weeks.Group E: 20ml of water daily as a control.Thirty-eight to forty weeks after the beginning of the administration, urinary bladder, kidney, liver, lung and lymph nodes were examined histologically.In groups A, C and D, papillomatous tumors of the urinary bladder were found in all of the animals and 27%, 90% and 100% of them were identified as cancer, respectively. The nature of the cancer was the transitional cell carcinoma in most cases and some of them were accompanied with squamous cell metaplasia.In the group B, hyperplasia of mucous membrane, papilloma and papillary cancer of the urinary bladder were seen in 4, 8 and 1 (8%) cases, respectively. The low rate of the development of the cancer in this group seems to be contrary to the expectation that a limited water supply would result in a greater rate of the development of bladder cancer owing to a long retention of concentrated urine in the bladder.The bladder carcinomas were transplanted subcutaneouslly into ACI/N rats. Palpable tumors developed in one week and the recipients died in 12 to 117 days.Sub-transplantations were all successful and 5 lines of transitional cell carcinoma and 2 lines of transitional cell carcinoma accompanied with squamous cell metaplasia were thus established.One of the transitional cell carcinoma with squamous cell metaplasia was transplanted intraperitoneally. A similar successful result was obtained.

Maxillary Antral Cancers

Cancer in the paranasal sinuses and nasal cavities in a relatively rare tumor disease, with an annual incidence of about one case per 100,000 inhabitants in Europe and the United States.1The majority of these tumors start in the mucous membrane of the maxillary antrum or the ethmoid labyrinth. A few cases originate from the nasal cavities, while primary cancers in the sphenoid and frontal sinuses are extremely rare. The age-specific incidence of the disease continuously increases with age; it is predominately a disease of the middle aged and aging. The only known etiologic factor of some importance in antral carcinoma is chronic sinusitis. Long-standing sinusitis causes a squamous cell metaplasia of the respiratory epithelium, which probably is the origin of most antral cancers. Some patients have a long history with signs of chronic sinusitis, prior to the signs of progressive tumor. Squamous cell carcinoma is the most frequent