Radiotherapy and skin tumors

Radiotherapy plays an important role in the treatment of skin tumours. For skin carcinomas, external irradiation (kilovoltage X-rays or electrons according to clinical characteristics) is more valuable than interstitial brachytherapy, which is recommended for tumours of the lip and of the nasal vestibule. In mycosis fungoides, total cutaneous electron beam radiation therapy is efficient for patients with limited superficial plaques. In the classical form of Kaposi's sarcoma, radiotherapy can achieve local control whereas it obtains good palliative results in the epidemic form.     

Synthesis of novel derivatives of aroylaminoalcohols and 3-amino-substituted 1-phenylpropanols with potential anti-inflammatory and immunomodulating activities

Considerable experience has been accumulated with low dose rate (LDR) brachytherapy in the treatment of squamous cell carcinoma of the oral cavity and oropharynx, 4 cm or less in diameter. Recent analysis of large clinical series provided data indicating that modalities of LDR brachytherapy should be optimized in treating these tumours for increasing therapeutic ratio. LDR brachytherapy is now challenged by high dose rate (HDR) brachytherapy and pulsed dose rate (PDR) brachytherapy. Preliminary results obtained with the last two modalities are discussed in comparison with those achieved with LDR brachytherapy.     

Chromosomal aberrations in couples undergoing intracytoplasmic sperm injection: influence on implantation and ongoing pregnancy rates

Mononitrosocaffeidine (MNC) and dinitrosocaffeidine (DNC) are new N-nitroso compounds obtained from in vitro nitrosation of caffeidine, a hydrolysis product of caffeine present in a typically made and widely consumed tea from Kashmir (India), a high incidence area of esophageal and stomach cancer. The chemical synthesis, in vitro metabolic studies and mutagenicity of the compounds has been previously reported. DNC, a nitrosamide is highly mutagenic both with and without metabolic activation whereas MNC, like several other aromatic asymmetric nitrosamines, does not exhibit genotoxic or mutagenic properties. We now report the results of the first carcinogenicity experiments on chronic oral administration of these compounds in BD-IX rats. The acute LD50 of MNC and DNC were about 1300 and 230 mg/kg b.w., respectively. Lung oedema and gastrointestinal haemorrhages were the first symptoms of intoxication observed after 2 days for both the compounds. All three dose groups of MNC treated rats showed localization of tumours in nasal cavity (93.9-100% of all malignant tumours). The tumours were histologically diagnosed as neuroepitheliomas of the olfactory epithelium (neuroblastoma of the bulbus olfactorii) and squamous cell carcinoma of the nasal cavity in the ratio of 3:1. No tumours of the nasal cavity were observed in the untreated controls. DNC, in contrast, induced squamous cell carcinoma of forestomach in 100% animals at low and high doses, of which nearly half the tumours metastasized predominantly into the peritoneum. No forestomach tumours were seen in the untreated controls. The data presented here clearly show the potential for induction of malignant tumours and distinct organ-specificity by MNC and DNC in rats, and support the postulate that a chronic exposure to these compounds may provide a carcinogenic risk for high incidence of gastrointestinal cancers in Kashmir.     

Salvage therapy of advanced squamous cell carcinoma of the mouth cavity and oropharynx. Results of interstitial high-dose-rate brachytherapy combined with ablative tumor surgery

PURPOSE: The clinical effect of high-dose-rate (HDR) interstitial brachytherapy combined with tumor resection was investigated in this retrospective study on patients with recurrent oral and oropharyngeal squamous cell carcinoma. PATIENTS AND METHODS: Oral and oropharyngeal squamous cell carcinoma in 38 patients were treated over a period of 7 years (1988-1994) by HDR interstitial brachytherapy using Gammamed 12i equipment. Pretreatment of patients in terms of irradiation and surgery differed (33 irradiated with a total dose between 60.0 and 75.6 Gy, including 8 patients with additional surgery; 1 patient with surgery alone, and 4 patients without any pretreatment). Indications for interstitial brachytherapy differed according to individual responses to treatment and medical histories. RESULTS: Interstitial brachytherapy was successful in the majority of patients, i.e. complete remission: 12, partial remission: 19, no change: 2, progression: 5. Local control and overall survival including patients with surgical treatment was 59% and 81% at 6 months and 47% and 49% after 12 months, respectively. CONCLUSION: Interstitial HDR brachytherapy with Iridium 192 is recommended in patients with local recurrences or second primary carcinomas after previous external radiotherapy in the head and neck region. Combination of interstitial brachytherapy and surgery is preferable for these patients.     

The pathology of the pulmonary arteries in lung tumors

A study was undertaken to analyse the type and extent of pathological changes in the pulmonary arteries in non-small cell malignant tumours of the lung. Large-section histological preparations were made from 33 squamous cell carcinomas and 30 adenocarcinomas (T1 and T2 tumours) and classified according to tumour margin area (zone 1), intermediate area (zone 2) and tumour centre (zone 3). Transmural tumour growth with intraluminal cell formations in the pulmonary artery branches were found in the centre of all adenocarcinomas and 86% of squamous cell carcinomas, involving subsegment, prelobular and lobular arteries. Obstructive and obliterative changes in the pulmonary arteries as the result of tumour compression and secondary fibrosing changes predominantly occurred in the centre of all tumours. They were less common and less marked in zones 1 and 2. -Pulmonary artery branches in lung tumours of stages T1 and T2 showed marked infiltrating, obliterative and secondary inflammatory changes as far as complete vascular occlusions. These observations indicate that cytotoxic drugs, introduced via the systemic circulation, cannot reach and therefore not exert their effects in extensive areas of tumour.     

Nasal cancer in a worker exposed to formaldehyde

Formaldehyde has not been established as a human carcinogen. Toxicological studies have, however, demonstrated that formaldehyde causes squamous cell carcinoma of the nasal cavity in rats. A case of squamous cell carcinoma of the nasal cavity occurred in a 57-year-old man who had 25 years of occupational exposure to low concentrations of formaldehyde in the textile-finishing industry.     

Cobalt 60 radiotherapy for treatment of squamous cell carcinoma of the nasal cavity and paranasal sinuses in three horses

Three adult horses underwent aggressive treatment of squamous cell carcinoma of the nasal cavity and paranasal sinuses, using course-fractionated cobalt 60 radiotherapy. Squamous cell carcinoma of the nasal cavity and paranasal sinuses is not commonly diagnosed in horses. Historically, horses with this type of neoplasm have not been treated or have undergone some form of surgery. The prognosis for long-term survival or cure has been poor. Long-term results of cobalt 60 radiotherapy were good to excellent and exceeded those usually reported for horses treated surgically. On the basis of these results, use of radiotherapy for these neoplasms is recommended.     

Human bladder cancer: evidence for a potential irritation-induced mechanism

Bladder cancer is one of the most common human cancers, constituting about 6% and 2% of all cancers among males and females, respectively. Over 90% of all bladder cancers are transitional cell carcinomas, with most of the remainder being squamous cell carcinomas. Smoking and occupational exposure to aromatic amines and other agents are most prominent among the risk factors identified. Inflammation of the bladder, largely by infection but also by stones or a combination of the two, may play some role in human bladder cancer development. The association between inflammation and cancer appears to be stronger for squamous cell than for transitional cell carcinoma. Stones and infection can be important factors in the development of bladder tumours in rodents, but the tumours are predominantly transitional cell rather than squamous cell carcinomas.     

Biological indicators of survival in patients treated by surgery for squamous cell carcinoma of the oral cavity and oropharynx

Squamous cell carcinomas of the head and neck are a heterogeneous group of tumours with regard to anatomical site, natural history and response to various treatments. Assessment of the role of biomarkers as indicators of prognosis or response to treatment is thus complex. In the last decade, different biomarkers have been investigated in the search for objective and reproducible indicators of prognosis. In 69 squamous cell carcinomas of the oral cavity or oropharynx from patients treated with radical surgery alone, we determined cell kinetics, evaluated as in vitro 3H-thymidine labelling index (TLI), p53, bcl-2 and glutathione S-transferase pi (GST pi) expression, by using immunohistochemical methods. The biological variables were unrelated to one another or to established clinical and pathological prognostic factors. Univariate analysis showed that a low proliferative activity was associated to a significantly higher risk of death than that observed in patients with a high TLI, whereas p53, bcl-2 and GST pi expression did not provide prognostic information. Multivariate analysis showed that cell proliferation, gender and nodal status retained their clinical relevance. In the subset of node-negative patients, TLI and p53 expression were indicators of survival. Moreover, the combined analysis of TLI and p53 expression identified a subgroup of node-negative patients with slowly proliferating and highly p53-expressing tumours who died within 1 year of radical surgery. These results indicate that in patients with operable oral cavity and oropharyngeal cancer, biomarkers can provide important information on clinical outcome.     

Histochemistry of mucin secreting components in mucoepidermoid and adenosquamous carcinoma of the oesophagus

AIMS: To determine the direction of differentiation of the mucin secreting components in a rare group of oesophageal tumours--oesophageal squamous cell carcinomas with prominent mucin secreting components (mucoepidermoid carcinomas and adenosquamous carcinomas). METHODS: In a review of 617 cases of primary carcinoma of the oesophagus, 16 cases of squamous cell carcinoma with prominent mucin secreting components were studied using a battery of histochemical techniques. RESULTS: The mucin produced by these tumours was mixed and included a variable content of enzyme labile sialomucin (positive for mucicarmine, periodic acid Schiff, and alcian blue, and sensitive to sialidase digestion and negative for high iron diamine-alcian blue). Retrospective analysis of endoscopic biopsy specimens taken from these tumours showed that mucin was present in five (42%) cases. CONCLUSIONS: The glandular component of this group of tumours histochemically differentiated in the direction of oesophageal glands: examination of the mucin secreting component in squamous cell carcinoma in resected specimens is therefore required for recording the true incidence of this type of tumour.     

Hybrid verrucous squamous cell carcinoma of sinonasal tract: a case report

Verrucous carcinoma is a variant of squamous cell carcinoma and should be distinguished from benign papilloma and well-differentiated nonverrucous squamous cell carcinoma. It is rare tumor of the sinonasal tract. Occasionally, conventional squamous cell carcinomatous components may be seen in verrucous carcinoma. This entity is called a hybrid verrucous squamous cell carcinoma. We report a case of hybrid verrucous squamous cell carcinoma occurring in the nasal cavity and paranasal sinus of a 67-year-old male. The removed mass shows the typical feature of verrucous carcinoma, but focally conventional squamous cell carcinomatous area is also noted. The treatment of this case follows verrucous carcinoma, but close follow up is mandatory because it may potentially spread to regional lymph nodes in contrast to pure form of verrucous carcinoma.     

The prognostic impact of metastatic pattern of lymph nodes in patients with oral and oropharyngeal squamous cell carcinomas

In patients with squamous cell carcinomas of the oral cavity and the oropharynx the presence or absence of nodal metastases still is the most important predictive factor. The discriminative significance of extracapsular spread and the influence of features of the primary tumor-such as size and depth of invasion-on metastatic pattern, treatment failure and survival were evaluated. Five-year postoperative follow-ups of 115 consecutively treated patients were studied retrospectively concerning the incidence of distant metastases, local and regional recurrences and the 5-year survival rate. Maximum depth of invasion of the primary tumor and lymph node metastases were evaluated on the basis of histological patterns, and patients were grouped according to their histological diagnosis. The T4 category has a plain discriminative influence on the incidence of distant metastases, recurrent tumors and survival rate in contrast to the other T sizes. The classification N0, intranodal growth and extranodal growth of lymph node metastases resulted in a 5-year survival rate of 67, 59 and 31%. According to the classification, 84, 87 and 59% were without nodal recurrence after 5 years, and 79, 82 and 46% without distant metastases. Size and depth of invasion of the primary tumor are not connected significantly with the occurrence of extracapsular spread. The status of the lymph nodes in squamous cell carcinomas of the oral cavity and the oropharynx metastases and in particular the capsular rupture has the most significant prognostic influence. The histological feature of extracapsular spread could distinguish reproducibly high risk patients with squamous cell carcinomas of the oral cavity and the oropharynx.     

5-hydroxytryptamine1A receptor-mediated effects on adenylate cyclase and nitric oxide synthase activities in rat ventral prostate

AIM: To investigate the patterns of expression of transforming growth factor alpha (TGF-alpha) and epidermal growth factor receptor (EGFR) in squamous metaplasia and squamous cell carcinomas of the urinary bladder with and without schistosomiasis. METHODS: Immunohistochemical study of the expression of TGF-alpha and EGFR in squamous metaplasias (n = 12) and various grades of squamous cell carcinomas (n = 21) of the bladder with and without schistosomiasis. RESULTS: Focal cytoplasmic and membranous positivity for EGFR and TGF-alpha was seen in all cases of squamous metaplasia. The markers were diffusely coexpressed in a concordant pattern in areas of hyperplastic keratinising squamous metaplasia. A similar pattern of positivity was seen in verrucous carcinomas (n = 2) and well differentiated squamous carcinomas (n = 6). Progressive loss of differentiation was associated with increasing loss of EGFR staining while TGF-alpha staining was retained. Squamous cell carcinoma in situ (n = 2) showed focal positivity for TGF-alpha and EGFR. There were no differences in staining patterns between cases with and without schistosomiasis. CONCLUSIONS: The coexpression of TGF-alpha and EGFR by well differentiated squamous cell carcinomas and hyperplastic keratinising squamous metaplasia is consistent with the active regulatory role exerted by this autocrine loop. There is regional absence of expression of EGFR but not of TGF-alpha in squamous cell carcinomas of lesser differentiation, suggesting heterogeneity of such control in these tumours. The focal expression of the two markers in squamous cell carcinomas in situ indicates a possible second pathway of oncogenesis for less differentiated tumours. These observations may have important implications for the effectiveness of putative growth factor based treatments.     

Small cell neuroendocrine carcinoma of the nasal cavity and paranasal sinuses

Small cell neuroendocrine carcinomas (SNECs) of the sinonasal tract are extremely uncommon tumors. We reviewed the clinicopathologic features of six cases of this neoplasm. There was no sex preponderance with three females and three males and a mean age at presentation of 51 years (range, 38 to 68). Two patients had disease limited to the nasal cavity, and in four the tumor involved the nasal cavity and maxillary or ethmoid sinuses. Involvement of the orbit was present in two patients. Surgery was the primary treatment. After a mean follow-up of 37 months, one patient died of local disease and liver metastases, four were alive with recurrent or metastatic disease, and one died of unrelated causes. The tumors were composed of sheets, nests, and trabeculae with extensive areas of necrosis and hemorrhage. The individual cells were small to intermediate in size and had scanty cytoplasm. The nuclei were oval or round and hyperchromatic with absent or inconspicuous nucleoli. Nuclear molding and crush artefact were present in five cases. All tumors had a high mitotic rate with frequent abnormal mitotic figures. All cases stained for Cam 5.2, neuron-specific enolase, and chromogranin. Five cases were positive for AE1:AE3, and four for synaptophysin. No case stained for S-100 protein, or neurofilaments. O-13 stained one case. No case contained EBV-RNA. SNECs of the nasal cavity and paranasal sinuses are aggressive tumors with pathological features similar to those of anaplastic small cell carcinomas of the lung. They exhibit morphological and immunophenotypic features different from olfactory neuroblastoma and should be distinguished from this tumor.     

Inverted papillomas in the nose and paranasal sinuses

Inverted papillomas in the nose and/or paranasal sinuses exhibit a high recurrence rate, and an association with malignancy. Early diagnosis and aggressive surgical therapy are thus essential. Seventeen cases of inverted papilloma seen at Saitama Cancer Center over a 17-year period were reviewed. Common presenting symptoms, the primary papilloma sites and the results of surgical treatment were as follows. 1) Almost all patients complained of nasal obstruction. The usefulness of nasal biopsy of the tumor was confirmed, with 12 cases being diagnosed as having inverted papilloma pre-operatively. Inverted papilloma without squamous cell carcinoma caused osseous thinning, but did not destroy the bone. 2) It was found that the primary site of the papilloma involved the lateral wall of the nasal cavity. Lateral Rhinotomy was therefore recommended as a standard treatment. 3) The recurrence rate was 1/12 after Lateral Rhinotomy. Two cases had complaints associated with the Lateral Rhinotomy, nasolacrimal duct stenosis, and a scar in the median corner of eye. 4) Only one case had concomitant squamous cell carcinoma in the nose and maxillary sinus. This patient received chemo therapy, radiation therapy and finally maxillectomy, but the inverted papilloma recurred several times. Six years later, squamous cell carcinoma recurred and lead to this patient's death.     

Heterogeneity of squamous cell carcinomas of the head and neck in relation to clinicopathological variables

We analysed 32 primary, 8 recurrent and 16 metastatic squamous cell carcinomas of the head and neck by flow cytometry to assess tumoural heterogeneity. Intratumoural heterogeneity was found in 9 of 30 primary tumours (30%). All heterogeneous tumours had diploid and aneuploid cell lines. DNA indices were different from those of the primary tumours in 3 of the 8 recurrent lesions (38%) and in 8 of the 12 metastatic lesions (67%). The results indicate that new cell lines evolve during the process of recurrence and metastasis. The incidence of recurrence, metastasis, and heterogeneity increased with the size of the tumour. Histologically, there were tumours in which the degree of differentiation and mode of invasion of primary lesions were not consistent with the results of flow cytometry in both homogeneous and heterogeneous tumours. In conclusion, multiple sampling for flow cytometric analysis is essential for better characterization of oral carcinomas.     

Genomic imprinting in the brain

Biopsies of cervix uteri from 166 patients with benign and malignant lesions (12 normal, 48 inflammatory lesion, 6 adenocarcinoma, 2 adenosquamous carcinoma and 98 from squamous cell carcinomas) were studied histochemically. The stains used were PAS with/without diastase, AB/PAS (pH 2.5) and OR/AB. In inflammatory lesions neutral mucin was predominent which was replaced by sialomucin and sulphomucin in endocervical polyps. In malignant lesions sulphomucin was predominent. Seventeen percent cases of squamous cell carcinomas needed reclassification after mucin staining. Of the fourteen large cell non-keratinizing squamous cell carcinomas, 12 were reclassified as squamous cell carcinoma with mucin secretion and 2 as adenosquamous carcinoma. One case of small cell non-keratinizing squamous cell carcinoma was reclassified as moderately differentiated adenocarcinoma. None of the keratinizing carcinomas had evidence of mucin secretion. Mucin histochemistry should be done routinely on non-keratinizing squamous cell carcinomas to pick up more cases of carcinoma with evidence of mucin secretion which can be missed on routine haematoxylin and eosin stains. Such carcinomas are known to pursue a more aggressive clinical course and have a poorer prognosis than non-mucin secreting type of squamous cell carcinoma.     

Use of flow cytometry in the analysis of stage III squamous cell carcinoma of the oesophagus and its association with MIB-1

AIMS: To examine the prognostic and pathobiological importance of DNA content in oesophageal squamous cell carcinomas in Hong Kong Chinese subjects; to evaluate its association with the immunohistochemical proliferative marker MIB-1. METHODS: Paraffin wax embedded tumour tissue and adjacent normal tissue (control tissue) samples from 45 resected stage III oesophageal squamous cell carcinomas were studied using flow cytometric analysis. The DNA content and the clinicopathological data of these patients were analysed together with the MIB-1 labelling index. RESULTS: DNA aneuploidy was present in 14 (31%) of the 45 cases. However, the DNA content did not correlate significantly with the age, sex, or survival of the patients, nor the length, location, differentiation and MIB-1 labelling index of the oesophageal carcinomas. The synthetic (S) phase fraction of diploid tumours bore no relation to the patients' survival or MIB-1 score. CONCLUSIONS: Flow cytometry was not as useful as the MIB-1 labelling index in predicting the biological characteristics of the tumours and the prognosis of patients with oesophageal squamous cell carcinomas. This study does not support the routine use of DNA flow cytometric analysis in oesophageal cancers.     

Ultrasonic endoscopy of superficial epidermoid cancer of the esophagus

Superficial squamous cell carcinomas of the oesophagus are defined as cancers confined to the mucosa or involving the submucosa but sparing the muscularis mucosae, with or without lymph node extension. Although lymph node involvement is rare (less than 5%) in tumours confined to the mucosa, it is frequent (30 to 45%) in tumours involving the submucosa, which have a prognosis similar to that of the usual obstructive tumours. Endoscopic ultrasonography is the most accurate examination (diagnostic accuracy greater than 95%) to distinguish between superficial and advanced cancers. The absence of visualization of the muscularis mucosae with the currently available transducers limits the decision-making value of such a distinction except in the case of flat tumours in which the absence of ultrasonographically detectable parietal thickening indicates the presence of a cancer confined to the mucosa, with an excellent prognosis.     

Paraspinal calcinosis associated with progressive systemic sclerosis. Case report

The incidence of basal cell carcinoma and squamous cell carcinoma (non-melanoma skin cancer) is increasing in the U.K., and the importance of this has been recognized in the 'Health of the Nation' target of halting the annual increase in the incidence of skin cancer by the year 2005. An accurate assessment of incidence is necessary both in meeting this target and in planning skin cancer services. We have examined the ways in which basal cell carcinoma and squamous cell carcinoma are diagnosed and treated in Greater Glasgow and have determined how many of these tumours are, recorded by the West of Scotland Cancer Registry. Our results show that there is under-registration of both basal cell carcinoma and squamous cell carcinoma. Overall, 39 of 127 basal cell carcinomas (31%; 95% confidence interval [CI] 23-39%) and 11 of 25 squamous cell carcinomas (44%; CI 26-63%) were not registered by the cancer registry. We also showed that dermatologists rarely treat clinically suspicious tumours without obtaining pathological proof of the diagnosis. Accurate data collection by selected representative cancer registries is suggested as a possible solution.