Effect of various forms of metastatic lymph node involvement on prognosis of squamous epithelial carcinomas of the upper aerodigestive tract

BACKGROUND: Based on a new histo-morphological rating scheme, we assessed the impact on patient prognosis of lymph node metastasis of squamous cell carcinoma (SCC) in the head/neck area. Special attention was given to possible capsular rupture. METHOD: In a retrospective study, 111 patients with squamous cell carcinoma of the head and neck with concomitant cervical lymph node metastases were evaluated to determine the importance of lymph node capsular rupture on the occurrence of disseminated disease, loco-regional recurrence as well as survival rate. To cover the broad morphological spectrum of cervical metastatic disease, a newly developed scheme (differentiating seven different histo-morphological types of lymph node metastasis) was applied. On the basis of this scheme, every single metastatic lymph node received a score from one to seven. These single scores were then added to obtain a total score for every individual patient. These total scores were then divided into four groups. RESULTS: Synthesis of histo-morphological pattern of metastasis in combination with the number of metastatic lymph nodes showed highest concordance/significance in respect of disseminated disease (p = 0.0029), local recurrence (p = 0.0008) and regional lymph node metastasis (p = 0.0000) as well as survival rate (p = 0.0000). CONCLUSION: The newly introduced histological scheme seems to provide more accuiate and detailed information on the prognosis of SCC in the head and neck area.     

Early invasive colorectal carcinomas metastatic to the lymph node with attention to their nonpolypoid development

Clinicopathologic study of six cases of early invasive colorectal carcinoma metastatic to lymph node was performed in order to elucidate possible characteristics relating to the risk of metastasis, with particular attention to the growth pattern of the primary tumor. All of the cases had at least one of the well-known risk factors for lymph node metastasis, including moderately or poorly differentiated histologic characteristics, considerable degree of submucosal invasion, and lymphatic invasion. An interesting finding of the present study was the identification of a nonpolypoid growth pattern with no concomitant adenomatous tissue, which seemed to be different from that of "malignant polyps" of previously reported cases showing adenoma-carcinoma sequence. This unique growth feature was found in all of the cases. Therefore, in addition to the accepted risk factors, nonpolypoid growth pattern and absence of adenomatous component may be risk factors predictive of nodal metastasis in patients with early invasive colorectal 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.     

A case-control study of element levels and cancer of the upper aerodigestive tract

A population-based case-control study was conducted in western Washington state to investigate possible dietary risk factors for laryngeal, esophageal, and oral cancers. Using results from a food frequency questionnaire, past dietary intakes of iron, zinc, and calcium were estimated for 661 cases and 466 controls. Clippings were also taken from the nails of both halluces to determine concentrations of iron, zinc, calcium, chromium, and cobalt in 507 of the cases and 434 of the controls. After adjustment for smoking, alcohol, and dietary beta-carotene and vitamin C intake, individuals who reported dietary intakes of iron and zinc in the upper quartile were less likely to develop cancers of the larynx and esophagus than were individuals with intakes in the lowest quartile [odds ratios (OR), 0.5 for iron and 0.1 for zinc]. However, there were no significant differences in zinc concentrations in nail tissue between subjects with these types of cancer and controls. Esophageal cancer cases had higher nail concentrations of iron and calcium than did controls (OR, 2.9 for high versus low quartiles of iron; OR, 2.6 for high versus low quartiles of calcium). Individuals who developed esophageal or oral cancer were more likely to have elevated cobalt concentrations in their nail tissue than were individuals without cancer (OR, 9.0 and 1.9 respectively, for high versus low quartiles). The results of this study suggest that there may be differences in mineral intake or metabolism between individuals who develop some carcinomas of the upper aerodigestive tract and those who do not.     

Cervical angiofollicular lymph node hyperplasia (lymphoid hamartoma)

A case of the hyaline vascular type of angiofollicular lymph node hyperplasia (lymphoid hamartoma) in the neck of a 25-year-old Hindu male is reported. A brief review of the literature is presented and relevant clinical, pathological and therapeutic aspects of this lesion are discussed.     

Regional lymph node metastasis from cutaneous squamous cell carcinoma

The phenotypes of various STAT knockout mice reveal an unexpected specificity in the biological roles of these molecules. The mechanisms involved in generating selectivity and modulating STAT activity have been the focus of intense studies. This work has led to the discovery of novel families of proteins that regulate Jak-STAT signaling. Recently, the structures of a STAT dimer/DNA complex and of the amino-terminal domain have been solved, providing new insights into the function of these versatile proteins.     

Distribution of Salmonellae in the digestive tract and lymph node of carrier-dogs

The genetic activity of the antimicrobial food additives AF-2 and H-193 has been investigated in Saccharomyces cerevisiae. The strains chosen for the present studies were D5 for the induction of mitotic recombinational events and XV185-14C for the induction of reversion of the mutants lys1-1, his1-7 and homs3-7. When three concentrations (25, 50 and 100 mug/ml) of AF-2 were used in the reversion system of strain XV185-14C, there was an increase in the frequency of hom+ and his+ revertants as a function of incubation time, while the lysine mutant exhibited a very low frequency of induced reversion. When AF-2 and H-193 were compared at the same concentration and exposure time, AF-2 exhibited a higher genetic activity in both systems than H-193. However, H-193 was genetically more active in inducing revertants than AF-2, when the comparison was made at the same survival level. Cells of both haploid and diploid strains were found to be more sensitive to inactivation by AF-2 than by H-193 It should be pointed out that the solubility of H-193 was lower (about 4 mug/ml saturation) than the solubility of AF-2 (120 mug/ml saturation). The haploid strain was more sensitive to both compounds than the diploid strain.     

Cervical lymph node metastasis as the first manifestation of localized extramedullary plasmacytoma

Two patients who had cervical lymph node metastases as the first symptom of a localized soft tissue extramedullary plasmacytoma of the epiglottis and nasopharynx, respectively, are described. Classical multiple myeloma was excluded by bone marrow biopsies and x-ray studies of the skeleton. In both patients, the primary tumor was diagnosed 2 years after excision of the cervical lymph node. One patient had a IgD, lambda myeloma protein in the serum and excreted lambda Bence-Jones protein into the urine. No M-component was found in the other patient. Both are living with a long survival of 8 and 4 years respectively. The presence of a cervical lymph node plasmacytoma should suggest an upper respiratory tract or oropharynx plasmacytoma rather than a primary lymph node plasmacytoma.     

Late functional outcome after reconstruction of the upper aerodigestive tract with free transplanted microvascular anastomosed jejunum

Since 1983, 90 autologous jejunal transplantations for reconstruction of the upper digestive tract have been performed in 89 patients (9 females, 80 males, average age 56.3 years). 73 patients were operated primarily, in 16 patients a recurrent tumor had been treated. One patient received a second jejunal graft after necrosis. In these heterogenous patients, the primary tumor was located in the hypopharynx 48 times, in the larynx 21 times, in the oropharynx 19 times and twice in the oral cavity. There was nearly always tumor stage III or IV without distant metastases. Following locoregional tumor resection, speech restoration was achieved 35 times by a siphon-like tube, and the upper digestive tract was reconstructed using a patch 18 times and by a tube 28 times. A combination of tube or patch with a siphon-like tube was employed 9 times. In only two of 16 patients with recurrent tumor, speech reconstruction was performed, in the other 14, the upper digestive tract was reconstructed. In those patients, in whom speech reconstruction (by siphon tube or by combination with tube/patch) was intended, this was achieved in 81.5%. Successful functional reconstruction of the upper digestive tract (by patch, tube, combination) could be achieved in about 60% of these patients.     

How tumor stage affects surgeons'' surveillance strategies after surgery for carcinoma of the upper aerodigestive tract

OBJECTIVE: To compare the expression of adhesion molecules on synovial T cells from patients with early spondyloarthropathy (SpA) and rheumatoid arthritis (RA), with special reference to the beta7 integrins alpha4beta7 and alphaEbeta7 in view of their intimate association with intestinal tissue. METHODS: Twenty-five synovial cell lines were generated by interleukin 2 (IL-2) expansion from synovial biopsies of patients with early SpA and RA, obtained from macroscopically inflamed synovial tissue by needle arthroscopy, and subsequently characterized by flow cytometry for CD3, CD4, CD8, L-selectin, CD11a, CD31, CD44, and alpha4beta7 and alphaEbeta7 integrin. RESULTS: In SpA, the beta7 integrin expression was increased, compared to RA. Furthermore, an inverse relation between alpha4beta7 and alphaEbeta7 was present in SpA (r = -0.75, p < 0.02), as on many mucosal T cells. In contrast, an opposite correlation was noted in RA (r = +0.84, p < 0.01), as similarly described on a subset of circulating T cells. CONCLUSION: Increased expression of beta7 integrins was noted on synovial T cell lines from SpA compared to RA, with discriminative correlations between alpha4beta7 and alphaEbeta7. This suggests a different origin of the synovial T cells in these diseases.     

Management of thyroid carcinoma invading the aerodigestive tract

OBJECTIVES: To evaluate approaches to thyroid carcinoma invading the aerodigestive tract, with particular attention to well-differentiated carcinomas. STUDY DESIGN: Retrospective review of experience with thyroid carcinoma invading the aerodigestive tract over a 20-year period at a tertiary referral hospital. METHODS: The medical records of all patients with a diagnosis of thyroid cancer treated at Emory University Hospital, Atlanta, Georgia, from 1977 through 1997 were reviewed. Multiple clinical variables were analyzed including treatment, development of recurrence, and survival. Survival and time to local recurrence were determined by Kaplan-Meier analysis, and statistical comparisons were made using log-rank analysis. RESULTS: Five hundred thirty-six cases were identified; 28 patients (5.2%) were identified with invasive disease involving the aerodigestive tract. Histologic findings at the time of invasion included 15 well-differentiated (WD) carcinomas and 13 poorly differentiated (PD) carcinomas. Eight of the 28 patients (5 WD, 3 PD) underwent surgical resection of some portion of the aerodigestive tract with curative intent. Ten patients (8 WD, 2 PD) underwent incomplete resection with tumor left adjacent to aerodigestive tract structures. All patients undergoing incomplete resection developed local recurrence. Six required salvage resection, as opposed to no recurrences in WD carcinomas following complete resection (P = .01). Survival at 5 years for WD carcinomas undergoing complete resection versus initial incomplete resection was 100% versus 50%, respectively (P = .27). CONCLUSION: Review of our experience shows that complete resection of thyroid carcinoma invading the aerodigestive tract can offer prolonged palliation, improved local control, and the opportunity for cure in selected patients.     

Expression of ICAM-1 in implanted primary and metastatic squamous cell carcinomas in rats

FF6 tumor cells are derived from a spontaneous rat squamous cell carcinoma (SCC) which originally arose in the facial skin of a DA rat. In this study, FF6 tumor cells were implanted into rat oral mucosa to establish an ex vivo metastatic model. We analyzed the expression of intercellular cell adhesion molecule-1 (ICAM-1) in the implanted primary and metastatic FF6 tumors by immuno-staining with a monoclonal antibody (mAb) against ICAM-1. The implanted primary FF6 cells showed strong expression of ICAM-1, whereas the tumor cells of metastatic lesions showed weak or negative expression of ICAM-1. By immunostaining with mAb OX6, a number of MHC class II-positive macrophages were detected in tumor mesenchyme and surrounding the metastatic foci. These results suggested that the local immune reaction in the lymph node influenced the expression of ICAM-1 on tumor cells, and that MHC class II-positive macrophages may play a role in transplanted tumor growth and metastases.     

Expression of CD44 variant exons by primary and metastatic oral squamous carcinomas

Abnormal CD44 expression in many neoplasms correlates with behaviour, but reports on its role in oral squamous carcinoma are contradictory. CD44 expression was characterised in a closely matched series of oral carcinomas with and without metastases in both frozen and formalin-fixed tissue and correlated with behaviour and histological grading parameters. Eleven primary oral squamous carcinomas without metastases and nine primary carcinomas with 19 matched metastases were stained immunocytochemically for CD44H and products of variant exons v3, v4/5, v6 and v9. Patterns of staining in frozen and formalin-fixed tissue were correlated with invasive front grading and behaviour using exact inferential statistics. Most primary carcinomas stained for all exons tested but some showed loss of expression of v4/5. Loss of expression was more marked in metastases, but there was no correlation between expression and behaviour or grade. Stromal surfaces of epithelial cells often expressed variant exon products reflecting loss of polarity. This, together with selective loss of v4 and v5 in primary carcinomas and their more frequent loss in metastases, suggests that CD44 may play a role in metastasis of some oral squamous carcinomas.     

Prognostic factors of cervical lymph node metastasis in head and neck squamous cell carcinoma

AIMS AND BACKGROUND: The metastatic spread of squamous cell carcinoma of the head and neck (SCCHN) to the cervical lymph nodes is a negative prognostic factor in terms of survival. We have used multivariate analysis to identify the possible prognostic significance of a number of clinical and pathological characteristics in relation to possible involvement of the cervical lymph nodes in a series of 396 patients. METHOD: 396 patients with SCCHN were studied. Variables regarding the patient, the carcinoma and histology were analysed by multivariate analysis using BMDP's PLR programme. RESULTS: Some variables appear to represent predisposing factors for tumor spread to the lymph nodes: tumor site (supraglottic larynx: P = 0.005; base of the tongue: P = 0.02; hypopharynx: P = 0.02), grading (P = 0.001), and a number of histological parameters (lower degree of histological differentiation: P = 0.001; vascular permeation: P = 0.04; perineural invasion: P < 0.05; prevalently plasmocytic infiltrate: P < 0.05). CONCLUSION: The identification of cases at risk for metastasis can be improved by the assessment of prognostic factors, with a consequent improvement in treatment strategies.     

Cervical lymph node metastasis disclosing a Grawitz's tumor. Apropos of a case

The authors report a case of advanced renal cell carcinoma presenting in the form of cervical lymph node metastases. In the absence of any specific clinical signs and an ENT portal of entry, this obviously neoplastic subdigastric lymphadenopathy was apparently primary. Histopathological examination of the cervical lymph node dissection revealed metastatic renal cell carcinoma and complementary investigations revealed the primary tumour in the right kidney. The course was fatal within several weeks despite treatment. The various problems raised by this truly metastatic disease are discussed.     

Polarographic detection of reoxygenation of lymph node metastases in the initial phase of primary radio- and radiochemotherapy in patients with advanced squamous epithelial carcinomas of the head and neck

Tyrosine phosphorylation is widely recognized as playing an important role in cell differentiation, proliferation and carcinogenesis. We used the polymerase chain reaction (PCR) method to identify protein tyrosine kinases that were expressed in the skin. Mixed oligonucleotide probes were used to amplify and screen neonatal murine skin mRNA for clones encoding amino acid contiguities, the conservation of which is characteristic of the protein tyrosine kinase family. When the PCR products were sequenced, a novel clone encoding protein tyrosine kinase, PTK70, was identified. A full-length cDNA was isolated from a mouse thymus cDNA library. The nucleotide and deduced amino acid sequence showed that it featured src-homology (SH) 2 domain, SH3 domain and kinase domain like other src family protein tyrosine kinases, but lacked the N-terminal myristylation site and C-terminal tyrosine residue. Although the mRNA of PTK70 was detected in various tissues ubiquitously, the degree of its expression differed among tissues. Murine skin is one in which PTK70 was expressed strongly, with its expression being much stronger in the epidermis and in the cell line derived from murine keratinocytes than in those from melanoma or fibroblast cell lines. These evidences suggest that PTK70 may be involved in proliferation or differentiation of keratinocytes in the skin.     

Four multiple primary malignant neoplasms of the aerodigestive tract

Multiple primary cancers of the head, neck, and upper aerodigestive tract have been documented in patients previously treated for oropharyngeal cancer. There generally is no causal relationship established between the different tumors. Two synchronous or metachronous cancers are common, three are unusual, and four are very unusual. We describe the treatment of a patient with tonsillar and synchronous esophageal and pulmonary cancers followed by a tongue cancer over a 6-year period.