Painful ophthalmoplegia following treated squamous carcinoma of the forehead. Orbital apex involvement from centripetal spread via the supraorbital nerve

Intraneural and perineural spread of squamous carcinoma from the face to the cranial cavity is an important cause of delayed cranial nerve palsies after local excision of a skin tumour. As exemplified in reports of two cases, signs of this type of centripetal spread of squamous cell tumour along the branches and trunk of the supraorbital nerve are (i) severe unremitting orbital and forehead pain with associated hypoaesthesia, (ii) palpable or radiological evidence of thickening of the nerve at the supraorbital notch and (iii) evolution of ophthalmoplegia, blindness, and sensory loss in the first division of the trigeminal nerve. Appearance of severe supraorbital neuralgia months or years after excision of a skin tumour from the forehead should alert the clinician to extension of tumour cells along the supraorbital nerve. This may enable him to institute timely treatment before a complete orbital apex syndrome has developed.     

Analysis of tumor-infiltrating lymphocytes in cutaneous squamous cell carcinoma

OBJECTIVE: To characterize tumor-infiltrating lymphocytes (TILs) within lesions of cutaneous squamous cell carcinoma (SCC) and related disorders. DESIGN: Case series with 1- and 2-color immunohistologic, molecular biological analysis of T-cell clonality and in vitro cytotoxicity assays. SETTING: Academic medical center. PATIENTS: Twenty-one patients, including 6 with actinic keratoses, 4 with SCC in situ, and 11 with invasive SCC. RESULTS: CD8+ TILs were present within lesions of cutaneous SCC and AK. These cells constituted a variable minority of the total T-cell infiltrate, and many expressed a phenotype consistent with major histocompatibility complex-restricted cytotoxic T lymphocytes: CD3+, TIA1+, CD16-, CD56-, CD57-. They also expressed HLA-DR, suggesting their activation in vivo. Virtually all T cells were T-cell receptor (TCR)-beta + delta, indicating that they expressed the TCR-alpha beta protein heterodimer. Molecular biological analysis of TCR-gamma gene rearrangements by the polymerase chain reaction and denaturing gradient gel electrophoresis technique indicated that the TILs were polyclonal. Functional studies suggested that TILs derived from SCC lesions were cytotoxic for autologous tumor cell targets. CONCLUSION: Tumor-infiltrating lymphocytes within cutaneous SCC lesions contain a subpopulation of polyclonal, major histocompatibility complex-restricted cytotoxic T lymphocytes expressing the TCR-alpha beta heterodimer.     

Nodal spread of squamous cell carcinoma of the oral cavity detected with PET-tyrosine, MRI and CT

The uptake of L-1-[11C]-tyrosine (TYR) in cervical lymph nodes of eleven patients with squamous-cell carcinoma (SCC) of the oral cavity was studied with PET to detect lymphogenic metastases. METHODS: The TYR-PET results were compared with clinical, MRI, CT, histopathologic findings and historical data of patients studied with FDG. Sensitivity, specificity, accuracy and the positive and negative predictive values were calculated. RESULTS: TYR-PET had sensitivity of 83% and a specificity of 95%. In contrast, the sensitivity and specificity for MRI were 33% and 96%, respectively. The sensitivity and specificity for CT were 55% and 91%, respectively. TYR-PET results compared favorably with FDG. CONCLUSION: With TYR-PET, SCC metastases of the oral cavity can be visualized with high sensitivity and specificity. TYR-PET can be an additional tool for further evaluation of neck malignancies.     

Aggressive cutaneous squamous cell carcinoma of the head and neck in patients with chronic lymphocytic leukaemia

We describe multiple cutaneous squamous cell carcinomas of the head and neck in five patients with chronic lymphocytic leukaemia (CLL). When associated with CLL, cutaneous squamous cell carcinomata behave in a much more aggressive manner than otherwise expected. Four patients developed local recurrence after primary treatment. All five patients developed lymph node metastases containing squamous cell carcinoma. Three of five patients (60 per cent) had multiple primary lesions. Whereas the increased incidence of second cancers in CLL and notably of skin cancers is documented, little has been written to describe the aggressive behaviour of these tumours. It is important, when treating these patients, to be aware of the high tendency towards local recurrence and lymph node metastasis and to consider an aggressive management plan and careful follow-up.     

A cell line (SCABER) derived from squamous cell carcinoma of the human urinary bladder

An established cell line derived from a documented squamous cell carcinoma of human urinary bladder is described. The cultured cells retained the characteristic morphology of the tumor of origin for 40 in vitro passages. Numerous desmosomes were found between cultured cells. Chromosome analysis showed hypotetraploidy with no obvious modal number, while distinctive marker chromosomes and a male karyotype were present.     

Expression of multidrug resistance-associated protein (MRP) in head and neck squamous cell carcinoma

Vascular parkinsonism is thought to be a distinct parkinsonian syndrome associated with small deep infarcts and white matter lesions (WMLs). We studied the prevalence of parkinsonian features (bradykinesia, rigidity, tremor, and gait disorder) in relation to small deep or territorial infarcts and WMLs on computed tomography (CT) in 62 lacunar and 41 territorial stroke patients, at 3.0 (median) years of follow up. One or more parkinsonian signs were found in 36% of these patients; 11% clinically had parkinsonism. Parkinsonian signs were found more frequently in lacunar than in territorial stroke patients: bradykinesia in 45% and 7%, rigidity in 13% and 7%, tremor in 6% and 7%, and gait disorder in 16% and 7%, respectively. Patients with WMLs at study entry (n = 16) were compared with those without WMLs (n = 87): 56% and 25% had bradykinesia, 25% and 8% rigidity, 25% and 3% tremor, and 38% and 8% gait disorder, respectively. Regression analysis with adjusted odds ratios ([a]OR) showed that WMLs at study entry were associated with bradykinesia ([a]OR 8.0, 95% confidence interval [CI] 1.6-41.6), gait disorder ([a]OR 7.1, 95% CI 1.5-33.7), and tremor ([a]OR 7.0, 95% CI 1.2-40.3). Bradykinesia was associated with lacunar stroke at study entry ([a]OR 11.5, 95% CI 2.4-54.9). Thus, one third of our stroke patients had one or more parkinsonian signs, and 10% clinically had a parkinsonian syndrome that differed from Lewy body parkinsonism: infrequent resting tremor, but frequent gait disorder. Parkinsonian signs were associated with WMLs and lacunar stroke. Therefore, this study favors a distinct vascular parkinsonian syndrome.     

Overexpression of scatter factor and its receptor (c-met) in oral squamous cell carcinoma

HYPOTHESIS: Scatter factor (SF) is a pleiotropic growth factor that recently has been shown to induce epithelial cell proliferation, random motility, and invasion via interaction with its receptor, a tyrosine kinase encoded by the c-met proto-oncogene. Studies involving a variety of solid tumors have suggested that overexpression of the SF/c-met ligand-receptor pair is associated with the acquisition of a malignant phenotype. We hypothesize that SF and c-met are overexpressed in epithelial malignancies of the head and neck including squamous cell carcinoma (SCC) of the oral cavity. STUDY DESIGN: Immunohistochemical staining of randomly selected normal, dysplastic, and malignant oral tissues. METHODS: Formalin-fixed, paraffin-embedded tissues were obtained from the Department of Oral Pathology at Shands Hospital (University of Florida), Gainesville, Florida. Examples of mild dysplasia, severe dysplasia, well-differentiated SCC, moderately differentiated SCC, and poorly differentiated SCC were randomly selected from the dictated reports of one of two staff oral pathologists. Histologically normal margins of each specimen served as normal controls. The tissues were immunohistochemically stained using commercially available antibodies against SF and c-met. Appropriate negative controls were run with each batch to ensure staining specificity. Evaluation of staining intensity was carried out using a computerized image analysis system. A one-way analysis of variance (ANOVA) with pairwise multiple-comparison procedures (Fisher method) was used to analyze the data. RESULTS: Statistically significant differences (P < .0001) in the intensity of staining were noted between the malignant and normal and the malignant and dysplastic tissues for both SF and c-met. No differences were appreciated when staining of normal and dysplastic sections of the SF-stained tissue were compared. CONCLUSIONS: The results suggest that the SF/c-met ligand-receptor pair is overexpressed in SCC of the oral cavity.     

Cutaneous horn and squamous cell carcinoma in situ (Bowen''s disease) in a cat

Cutaneous horn and squamous cell carcinoma (SCC) in situ (i.e., Bowen's disease) were documented concurrently in a cat. The cat had multiple, crusted lesions and a cutaneous horn on the right dorsal lumbar area. All the crusted cutaneous lesions were diagnosed as SCC in situ. Other findings included the presence of a thymoma and hepatoma. This cat was tested, and results were negative for feline leukemia and feline immunodeficiency viruses. At necropsy (eight months after the initial diagnosis was made) the hepatoma had ruptured, resulting in exsanguination and death.     

Metallothionein and Fas (CD95) are expressed in squamous cell carcinoma of the tongue

Metallothionein (MT) is a chelator present in myoepithelial cells, whilst the Fas-receptor (APO-1, CD95) has been described primarily in human T Jurkat cells. 20 cases of carcinoma of the tongue were investigated immunocytochemically with regard to MT, Fas and Bcl-2. In normal oral squamous epithelium, MT is located in the basal/parabasal dividing cells only. In well-differentiated nests of carcinomas, MT is observed almost entirely in peripherally located cells. In situ end-labelling indicates apoptosis in the centre of these nests, but not in the peripheral areas. Less-differentiated areas show more general MT-positivity, but little apoptosis. All 24 tumours are Fas-positive, but normal epithelia are mainly negative (P < 0.0001). Bcl-2 protein was sparse in the tumours compared with MT and Fas (P < 0.0001). We thus suggest that MT, possibly due to its chelating properties, may contribute to delaying cells entering apoptosis, both in normal epithelium near the base and in less-differentiated regions of carcinoma. Moreover, Fas may be present in cells of human malignancies, as well as those of established malignant cell lines.     

Immunohistochemical characterization of transplantable rat squamous cell carcinoma (FF-6) in skin and thymus

FF-6 is a transplantable squamous cell carcinoma which originally arose in the facial skin of a DA rat. It was established after maintaining the tumor in the subcutaneous tissue or peritoneal cavity of DA rats conventionally for over 30 generations. When the soybean-sized original FF-6 tumor was transplanted subcutaneously, it became an oval, hard, whitish, solitary and thumb-head-sized nodule within one month. After intraperitoneal transplantation of FF-6, it formed many nodules ranging from miliary to thumb-head size, which adhered and/or metastasized to many abdominal organs. When FF-6, cut into small pieces, was injected into the lower lip, the tumor grew bigger in situ, and metastasized to regional lymph nodes. Histologically, FF-6 was characterized as a well-differentiated squamous cell carcinoma, showing positive staining with anti-keratin, anti-laminin, anti-collagen type IV, anti-fibronectin and UB-14 antibodies. This transplantable tumor may be useful for analyzing the mechanisms of proliferation and metastasis of squamous cell carcinoma in vivo, and the host defence mechanism in rats, as well as being a suitable model of human squamous cell carcinoma.     

Retinoic acid and N-(4-hydroxy-phenyl) retinamide suppress growth of esophageal squamous carcinoma cell lines

The roles of endogenous serotonin (5-HT) and 5-HT receptor subtypes in regulation of acetylcholine (ACh) release in frontal cortex of conscious rats were examined using a microdialysis technique. Systemic administration (1 and 3 mg/kg, i.p.) of the 5-HT-releasing agent p-chloroamphetamine (PCA) elevated ACh output in a dose-dependent manner. Depletion of endogenous 5-HT by p-chlorophenylalanine significantly attenuated the facilitatory effect of PCA on ACh release. The PCA (3 mg/kg)-induced increase in ACh release was significantly inhibited by local application of the 5-HT4 receptor antagonists RS23597 (50 microM) and GR113803 (1 microM), while the 5-HT1A antagonist WAY-100135 (10 mg/kg, i.p.; 100 microM), 5-HT(1A/1B)/beta-adrenoceptor antagonists (-)-pindolol (8 mg/kg, i.p.) and (-)-propranolol (150 microM), 5-HT(2A/2C) antagonist ritanserin (1 mg/kg, i.p.; 10 microM) and 5-HT3 antagonist ondansetron (1 mg/kg, i.p.; 10 microM) failed to significantly modify the effect of PCA. These results suggest that PCA-induced enhancement of 5-HT transmission facilitates ACh release from rat frontal cortex at least in part through 5-HT4 receptors.     

Cytotoxic and anti-proliferative effects of high-energy pulsed ultrasound (HEPUS) on human squamous cell carcinoma cells as compared to connective tissue fibroblasts

The cytotoxic and anti-proliferative effects of high-energy pulsed ultrasound (HEPUS) on human squamous cell carcinoma cells cloned from the hypopharynx (FaDu) and benign connective tissue cells (fibroblasts) were investigated in vitro. Sonication was carried out using an experimental piezoelectric, self-focusing burst-signal transducer. To increase the induction of cavitation, the transducer used was specifically designed to produce multiple oscillations with a high negative pressure amplitude. In both cell lines tested, the application of 100, 800 and 2000 pulses resulted in a high reduction of vital cells. After 2000 pulses, 4.0 +/- 1.1% of the fibroblasts but only 2.0 +/- 0.4% of the FaDu cells survived HEPUS exposure. A postexposure inhibiting effect of HEPUS for 10 days on the proliferation of surviving cells was noted for the FaDu cells exposed to 2000 pulses, but not as much for the fibroblasts. These findings support the hypothesis that human squamous cell carcinoma cells of the hypopharynx might be more sensitive to HEPUS than fibroblasts and that total tumor cell ablation might be possible in vitro given a sufficient number of HEPUS pulses.     

Demographic characteristics, pigmentary and cutaneous risk factors for squamous cell carcinoma of the skin: a case-control study

We conducted a case-control study of squamous cell carcinoma of the skin (SCC) in a cohort of people followed from 1987 to 1994. Subjects were residents of Geraldton, Western Australia, who were between 40 and 64 years of age in 1987. On 2 occasions, in 1987 and 1992, dermatologists examined participants for skin cancers. Subjects were also asked on several occasions about skin cancers that they had had treated. Migrants to Australia had reduced risks of SCC. Furthermore, people who migrated to Australia early in life or, equivalently, lived in Australia for a long time had a higher risk than immigrants who arrived later in life or more recently. People who had southern European ancestry had a much lower risk of SCC than other subjects, most of whom were of British or northern European origin. Among Australian-born subjects of British or northern European ancestry, the skin's sensitivity to sunlight was strongly associated with SCC. The pigmentary traits of hair colour, eye colour and skin colour showed weaker associations. The degree of freckling on the arm was strongly predictive of risk. The risk of SCC increased strongly with increasing evidence of cutaneous solar damage and was most strongly associated with the number of solar keratoses. Our results show that sensitivity to sunlight and high levels of exposure to sunlight are important determinants of the risk of SCC.     

Giant cell arteritis manifesting as chronic cough and fever of unknown origin

A 57-year-old white man sought medical attention because of chronic cough and fever of unknown origin. An extensive work-up over 4 weeks, including repeated blood cultures, chest roentgenograms, a gallium scan, and computed tomographic scans of the sinuses, chest, and abdomen, was nondiagnostic. The patient was referred to our institution for bronchoscopy. Further analysis of his history revealed that he had a headache in conjunction with the cough and an episode of a flashing color design in his left eye 1 week before assessment. The erythrocyte sedimentation rate was 115 mm in 1 hour. A biopsy of the temporal artery showed granulomatous inflammation of the vessel wall with multinucleated giant cells, histiocytes, lymphocytes, plasma cells, and few eosinophils. The multinucleated giant cells were closely related to the fragmented elastic lamina. Corticosteroid therapy resulted in prompt resolution of the chronic cough and fever. Giant cell arteritis should be considered in the differential diagnosis of chronic cough.     

Clubbed fingers and arthralgia as a reversible paraneoplastic syndrome (Pierre-Marie-Bamberger syndrome) in non-small-cell bronchial carcinoma

HISTORY AND CLINICAL FINDINGS: During chemotherapy for a non-small-cell bronchial carcinoma with metastasis to the right femur (previously locally excised), a 34-year-old man suddenly developed severe, lasting joint pain in the ankle, knee, elbow and wrist without signs of increased warmth or swelling of these joints. At the time of diagnosis clubbed fingers had been noted. INVESTIGATIONS: Radiography of the hands showed bilateral periosteal hyperostoses. Computed tomography of the thorax revealed tumor progression. DIAGNOSIS, TREATMENT AND COURSE: The triad of clubbed fingers, periosteal hyperostoses and arthralgia/arthritis with the pulmonary findings established the diagnosis of hypertrophic pulmonary osteoarthritis (HPO; Marie-Bamberger syndrome). Initially there had merely been the signs of the much more frequent incomplete form with only the clubbed fingers, the complete form developing with progression of the disease during chemotherapy, joint pains dominating the symptoms. After right upper lobectomy (primary adenocarcinoma) the joint pains ceased and the finger clubbing regressed. CONCLUSIONS: Only 10% of non-small-cell bronchial carcinomas are associated with HPO. Conversely, such a tumor is found in 90% of HPO of recent onset and should therefore be sought of when searching for the primary tumor. The signs of HPO are reversible if the underlying disease is adequately treated.