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In a 20-year-old female patient a small tumor (3 mm in diameter) was found in the upper nasal quadrant of the left conjunctiva bulbi. Lymphangiography showed that the conjunctival lymph vessels were ectatic. The histological study identified the excised material as tissue of the lacrimal gland.
Vessels within the lymphocytic infiltrate in 161 examples of 24 different diseases have been studied using light and electron microscopy and histochemistry. Hitherto undescribed venules have been identified within lymphocyte aggregates which exhibit a structure, ultrastructure and cytochemistry previously believed to be restricted to the high endothelial venules of lymphoid tissues. The significance of these findings is discussed within the context of lymphocyte migration into abnormal tissue.
Current conventional forms of cancer treatment represent non-specific modalities that destroy not only cancerous but also non-cancerous tissue in an effort to totally eradicate the neoplasm. It was unknown in head and neck cancer whether a more specific form of treatment, as it relates to neck nodal disease, was advisable. The purpose of this investigation was to study the cervical node immunoreactivity in head and neck cancer patients as a means of determining their immunologic capabilities and thus provide information about the merits of specific vs. non-specific cancer treatment. The results demonstrated that lymphocytes arising from cervical nodes caused alterations in the tumor growth. There appeared to be no particular difference in immunoreactivity of lymphocytes arising from nodes located in different areas of the neck. The regional immune system of neck nodes in the head and neck cancer patient appears to be capable of mounting an immune response irrespective of the patient's tumor status. Usual measures of systemic immunocompetence failed to identify any patients with advanced stage disease and showed little correlation with the regional immunoreactivity. The regional nodal immunoreactivity also did not correlate with the size or the numbers of metastatic neck nodes. The results demonstrate that cervical neck nodes are capable of mounting an immune response to head and neck cancer and are not mere passive filters that are periodically involved with tumor emboli. These results support the need for the development of reliable treatments which are directed at tumor tissue only.
Lymphangioma (LA) and congenital pulmonary lymphangiectasis (CPL) are part of a spectrum of lymphatic disorders less well characterized than other vascular tumors and malformations. Recent studies showed proliferative and involutional growth phases for hemangiomas that distinguish them from malformations. We investigated immunohistochemical reactivity and proliferative activity to determine whether a similar diagnostically/prognostically useful pattern exists for LA, comparing LA with CPL as a malformative lesion. Immunohistochemical tests for vimentin, Factor VIII-related protein, CD31, CD34, CD45RO, smooth muscle actin, Type IV collagen, MIB-1, bcl-2, and topoisomerase IIalpha were performed on 20 LAs and 10 cases of CPL. Giemsa staining was also performed to quantitate mast cells. Clinicopathologic correlation was performed by medical record review. LA and CPL shared a similar immunohistochemical profile for vimentin, Factor VIII-related protein, CD31, CD34, smooth muscle actin, CD34, and, to a lesser extent, CD45RO. CD31 and CD34 displayed the most uniform pattern of endothelial reactivity, although CD34 had high background staining. bcl-2 was negative. Four LAs exhibited focal low reactivity for MIB-1 and topoisomerase IIalpha; recent infection and thrombosis were associated conditions. LAs displayed seven-fold more mast cells and more reactive T lymphocytes than did cases of CPL. LA and CPL had similar immunohistochemical profiles; LA resembled vascular malformations more than hemangiomas. CD31 and CD34 were useful for detection of small lymphatics at resection margins of LA, a feature associated with recurrence. MIB-1 and topoisomerase IIalpha expression were associated with inflammatory, thrombotic, or reactive processes and were not diagnostically useful. Abundant mast cells, which also were noted in other soft tissue neoplasms, prompt speculation concerning their role in the growth of LAs.
OBJECTIVE: To explore the clinical manifestations of pulmonary lymphangitic carcinomatosis (PLC), to analyse its associated diagnostic methods, and to improve the understanding of PLC and its diagnosis. METHOD: Retrospective analysis of 4 cases of PLC and review of the literature. RESULT: The clinical manifestations of PLC include: (1) dyspnea and cough; (2) normal or restrictive pattern ventilation; (3) diffuse or local reticulonodular infiltrates in the lung like interstitial fibrosis and pleural effusion on chest radiograph; (4) CT and high-resolution CT (HRCT) scans reveal a beaded chain appearance caused by uneven thickening of the interlobular septa and pleural membrane, polygonal thickening of bronchovascular bundles, and mediastinal lymphadenopathy as well. CONCLUSION: These clinical data suggest that any manifestations similar to pulmonary interstitial fibrosis complicated with pleural effusion and paratracheal lymphadenopathy should be further differentiated from PLC by HRCT and pleural-lung tissue biopsy.
The axillary lymph-node-status is the most important prognostic factor in breast cancer patients without distant metastases. The proportion of node positive axillae depends on the number of histologically documented nodes (at least 6 according to TNM recommendations). The prognostic significance of solitary micro-metastases and of metastases detected only by serial sectioning or by immunocytochemistry is not yet established. An important prerequisite for successful conserving breast-cancer treatment is patient selection. Selection leads to a high proportion of patients with favourable prognosis: primary tumors less than 3 cm in diameter, at least 2/3 without axillary lymph-node-metastases, at least 1/3 less than 50 years old. That means attribution of prognostically less favourable patients to mastectomy. Tumor diameter and grading are established prognostic parameters of the primary. The significance of grading is independent of the system used and also independent of the reproducibility by different investigators. Measurement of tumor cell ploidy, proliferation and of epidermal growth factor-receptor content may add to the safety of prognosis prediction. Steroid hormone receptor content, eventually also Somatostatin-receptor and Aromatase activity in the tumor tissue can influence the therapeutic decisions.
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Fibrin plate was used to determine plasminogen activator (PA) of the head and neck tumor tissue. The results revealed: 1. The specific activity of PA of primary malignant tumor and neck lymphatic metastatic nodes were higher than that of normal tissue near cancer and benign tumor tissue; 2. The specific activity of PA was enhanced as advance of tumors in clinical stage. This study implicated that PA released from cancer cells can catalyze and convert plasminogen to plasmin, which results in tissue degradation, invasion and metastasis of tumor.
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BACKGROUND: Hepatocellular carcinoma (HCC) occur in livers with injury-remodeling, accomplished by enzymes called matrix metalloproteinases (MMP). Metastasis involves basement membrane invasion also caused by MMP activity. Alterations in MMP expression and their endogenous inhibitor (TIMP) may factor in HCC metastasis. METHODS: HCC specimens and lymph nodes (n = 7), and normal lymph tissue from organ donors (n = 8), were snap-frozen in liquid nitrogen and the mRNA precipitated. A series of reverse transcription-polymerase chain reactions (RT-PCR) were performed using MMP (MMP2, MMP7, MMP9) primers and TIMP (TIMP1, TIMP2) primers. These were semiquantitatively analyzed by comparing concentration with constitutive GADPH expression. RESULTS: There is an increase in MMP2:TIMP2 mRNA expression ratio in the normal and tumor margin tissue compared to the tumor. There are increases in all MMP and TIMP mRNA expression (except TIMP1) and alterations in all of the MMP:TIMP expression ratios in the draining lymph node. CONCLUSIONS: Alterations exist in MMP2:TIMP2: expression at the margin, and all of the MMPs in the draining lymph nodes. This likely reflects a host-tumor interaction that regulates tumor metastasis.
Improved extraction techniques combined with sensitive real-time reverse transcriptase-polymerase chain reaction may allow detection of mRNA in formalin-fixed, paraffin-embedded (FFPE) materials, but the factors affecting mRNA quantification in clinical material using these methods have not been systematically analyzed. We designed analyses using real-time reverse transcriptase-polymerase chain reaction for quantification of MART-1, beta-actin, and beta(2)-microglobulin mRNAs. The analytical intra- and interassay imprecision (coefficient of variation) was in the range 10 to 20% for all three genes studied. Using these protocols, we studied the influence of tissue autolysis and length of formalin-fixation on mRNA detection in metastatic melanoma. Delay in freezing reduced detectable mRNA, although this was less than predicted and mostly occurred early in autolysis. MART-1, beta-actin, and beta(2)-microglobulin mRNAs were consistently detected in FFPE metastatic melanoma even after fixation for up to 3 weeks, although the total mRNA detected was markedly reduced in fixed compared with fresh tissues (up to 99%). Quantification of MART-1 was, however, possible if this was expressed relative to a housekeeping gene. The polymerase chain reaction product from FFPE tissues could be increased up to 100-fold amplifying short (<136 bp) compared with long amplicons. Variations in time before tissue processing and in fixation length seem to be less important sources of imprecision than previously assumed. Our findings suggest that quantitative analysis of mRNA in archive and routine diagnostic tissues may be possible.
The introduction of Positron Emission Tomography (PET) and the use of the glucose analog F-18-Deoxyglucose (FDG) can help to improve the sensitivity of the diagnosis of lymph node metastases. Sensitivity exceeding 90% can be achieved when advanced imaging protocols and image reconstruction methods are used for PET. Superior staging information is obtained with PET as compared to morphological imaging methods for the most frequent tumor types. The accuracy of N-staging can be significantly improved by adding PET to the pretherapeutic diagnostic procedures. Limitations exist with regard to false positive results. Acute or chronic inflammation as well as unspecific reactions following radiotherapy may mimic tumor tissue.
The TNM staging system is a modus for diagnosis and treatment in which T is the extent of the tumor involvement, N is lymph node involvement, and M is the metastases; this system is supplemented with a histologic malignancy grade. Staging systems identify specific prognostic factors with which to predict clinical outcome. Staging systems are useful for assigning treatment priorities, determining the role of adjuvant therapies, and evaluating clinical investigations. Unfortunately, no universally accepted staging system for soft-tissue sarcomas exists. This is related to the relatively low incidence of sarcomas, the unique and unpredictable behavior of sarcomas, significant disagreement regarding histogenesis and grading, and lack of consensus regarding the value of various prognostic factors. In adults, the two most commonly used staging systems are those developed by the American Joint Committee on Cancer and by Enneking. In children, the Intergroup Rhabdomyosarcoma Study and the International Union Against Cancer have described the systems most commonly used. These systems for soft-tissue sarcomas rely on an ability to accurately determine both the local and distant extent of disease. Advances in the field of computed tomography and magnetic resonance imaging have made this possible. It is likely that a staging system based upon a more sophisticated understanding of the basic biology of sarcomas will become available.
5% of all malignancies involve the oral cavity. One percent of these malignancies are secondary to neoplasms that are usually found below the level of the clavicles. As it is widely accepted that the jaws do not contain a lymphatic system, it is believed that metastases there occur via the blood stream, a fact that is supported by the occurrence of metastatic foci in areas where spongiosa and slowing of the circulation favour the entrapment of metastatic emboli. This however does not explain why most of the metastases occur in the lower jaw (and in particular in the premolar-molar area) and not in the maxilla, where the spongiosa is more abundant. Batson's plexus has also been mentioned as a possible route of metastasis to the head and neck, thus explaining why, in some cases of metastases, the lungs are not involved, as the blood has not been filtered through the pulmonary bed before reaching the head and neck. In our review of the literature we found 422 metastatic lesions in the mouth, jaws and the surrounding tissues in 365 patients equally divided between men and women. 56.5% of the cases were above the age of 50. In 228 cases there were other metastases as well, whereas in 114 cases the only metastasis found was the one under study. In 22% of the cases, the metastatic focus in our area was the first indication of the existence of an undiagnosed primary malignant tumour somewhere else.(ABSTRACT TRUNCATED AT 250 WORDS)
Oestrogen receptors (ER) and progesterone receptors (PR) have been reported by several authors in the stromal cells of the human prostate. Controversial results exist on the expression of ER and PR in epithelial cells of the prostate. Some recent publications, in contrast to previous findings, have suggested that these receptors are also present in human prostate cancer cell lines derived from metastatic lesions. The expression of ER and PR in these cell lines has been re-examined to determine their presence in lymph node metastases from patients who did not receive any kind of endocrine therapy and in distant metastases obtained from patients who failed endocrine treatment. ER and PR expression in LNCaP, PC-3, and DU-145 cells was assessed by means of the reverse transcriptase-polymerase chain reaction, ligand binding assays, and immunohistochemistry. With all the techniques applied, the three cell lines were found to be negative for both ER and PR. Immunohistochemical analyses were performed in four lymph node metastases obtained at radical prostatectomy from patients who did not receive endocrine therapy and in 17 distant metastases obtained at palliative surgery from patients who failed endocrine therapy. All 21 metastases were negative for ER and PR on immunohistochemistry. These results do not support the recently developed concept that receptors for oestrogenic and progestagenic steroids are present in metastases from human prostate cancer.
The prognosis for patients with squamous carcinomas of the head and neck region is strongly influenced by the presence or absence of cervical lymph node metastases. Biological markers that indicated a high risk of metastasis would have a major role in determining the optimal therapeutic strategy for these patients. This editorial discusses recent studies of molecular and genetic markers of squamous carcinomas in relation to metastatic potential and highlights some of the issues that limit current progress in this field of study.
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