Cancer metastases to the cervical lymph nodes in an unknown primary location of the tumor

Out of 120 patients hospitalized with the diagnosis of metastases to the cervical lymph nodes and unknown primary location of the tumor, tumors were detected in 29 and lymphosarcoma in 10. In 24 (82.7%) patients the tumor was located in the upper respiratory tract and gastrointestinal tract. Malignant tumors of the naso- and stomatopharynx and vestibular part of the larynx most often metastasize into the lymph nodes. Radiotherapy was administered to all 81 patients with metastases and unknown location of the primary tumor and to 10 patients with lymphosarcoma of the cervical lymph nodes. The protocol of radiotherapy took account of the site of the metastases and probable primary tumor. A radical course provides cure in 15% of cases, as shown by follow-up of at least 2 years.     

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.     

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.     

MR imaging in squamous cell carcinoma of the head and neck with no palpable lymph nodes

PURPOSE: To assess the efficacy of MR imaging in the detection of lymph node metastasis in patients with no palpable lymph nodes ("N0 neck") who have squamous cell carcinoma of the head and neck region. MATERIAL AND METHODS: MR neck imagings in 18 patients who underwent neck dissection (bilaterally in 2) for squamous cell carcinoma of the head and neck region were examined preoperatively for the purpose of detecting lymph node metastases. The imaging features taken into consideration were: size (cutoff point 10 mm), grouping, presence of central necrosis, and appearance of extracapsular spread. The MR examinations comprised spin-echo T1- and T2-weighted sequences. The MR findings were compared with those of surgery and histopathological examination. RESULTS: MR suggested metastatic lymph node involvement in 5 necks. In 2 of these, central necrosis was seen in the enlarged lymph nodes. In a third, a grouping of the lymph nodes was noted. Extracapsular spread was not present. Histopathological examination revealed metastatic lymph nodes in 7 of the 20 necks, the rate of clinically occult disease being 35%, and 4 of them had been accurately graded by MR. There was one false-positive MR examination. The MR sensitivity was 57.1% and specificity 92.3%. CONCLUSION: MR may reveal metastatic lymph nodes in patients with no clinical evidence of metastasis. However, conventional MR techniques are not always sufficient for decision-making on surgery in cases of "N0 neck".     

Micrometastasis and tumor cell microinvolvement of lymph nodes from esophageal squamous cell carcinoma: frequency, associated tumor characteristics, and impact on prognosis

BACKGROUND: The purpose of this study was to investigate micrometastasis (MM) and tumor cell microinvolvement (TCM) in the regional lymph nodes of patients with esophageal squamous cell carcinoma (SCC). METHODS: MM was defined as individual tumor cells or tumor cell clusters <0.5 mm in greatest dimension with a surrounding stromal reaction. TCM was defined as individual tumor cells or tumor cell clusters without a surrounding stromal reaction. One thousand nine hundred and fifty-four lymph nodes were dissected from 69 complete (R0) resection specimens of TNM classified pT1-3, pN0 or pN1, and M0 esophageal SCC. These lymph nodes were examined immunohistochemically using the monoclonal antibody cocktail AE1/AE3 for cytokeratins. The primary tumors were immunostained with an anti-E-cadherin monoclonal antibody. RESULTS: MM +/- TCM was found in 13 cases (31.7%) and TCM alone in 2 cases (4.9%) of the 41 pN0 cases. The pN0 patients with MM (but not TCM) had the same shorter survival as the original pN1 cases (P < 0.05). Of the 69 primary tumors, 49 (71.0%) had reduced or negative E-cadherin expression that showed a correlation with the occurrence of lymph node metastases (original pN1), MM, and TCM, but not prognosis. CONCLUSIONS: The results of the current study show that, in SCC of the esophagus, MM, but not TCM, in the regional lymph nodes is prognostically equivalent to metastasis and should be examined by immunohistochemistry to classify these cases correctly as pN1.     

Metastasis of an adenocarcinoma of unknown origin to mediastinal lymph nodes, and transient regression

A 67-year-old woman was admitted to our hospital because of fever. Chest roentgenogram showed an enlargement of mediastinal lymph nodes. Despite thorough examination, no definite diagnosis could be made. The mediastinal lymph nodes got smaller over the next 3 weeks and a chest roentgenogram taken 4 months later showed no mediastinal lymphadenopathy. The mediastinal lymphadenopathy and fever recurred 5 months later. She underwent thoracotomy and the mediastinal lymph nodes were excised. Microscopic examination of pretracheal lymph node specimens showed invasion of poorly differentiated adenocarcinoma associated with abundant tumor-infiltrating lymphocytes. The other lymph nodes showed sarcoid reaction. Although she has been followed for one year and 11 months, no primary site of the cancer has been found. Metastasis of cancer of unknown origin to mediastinal lymph nodes is extremely rare. It is also interesting that the lymph node swelling diminished spontaneously. The tumor-infiltrating lymphocytes and sarcoid reactions may have been immunological responses to the cancer and may have caused the transient regression.     

Clinicopathological study on patterns of cervical lymph node metastases from squamous cell carcinomas (SCC) of the head and neck

In order to investigate the patterns of cervical lymph node metastases from head and neck SCC, serial sections were performed on 384 radical neck dissection (RND) specimens. Positive lymph node was found in 60.4% RNDs. The cervical lymph node spread from SCC in the head and neck regions including oral cavity, oropharynx, hypopharynx and larynx has some predictable patterns, i.e., for primary SCC of the oral cavity, the majority of cervical lymph node metastases were clustered at levels I, II and III; and for primary carcinoma of the oropharynx, hypopharynx and larynx, a majority of node metastases were located at levels II, III and IV. The positive lymph nodes mainly distributed at only one level or consecutive levels. The rates of pathologically positive lymph node and extranodal spread grew with the increase of the clinical N-staging. It is suggested that supraomohyoid neck dissection (levels I, II and III) is particularly applicable to carcinomas of the oral cavity, and lateral neck dissction (levels II, III and IV) is applicable to carcinomas of the oropharynx, hypopharynx and larynx in patients with limited (N0 and N1) neck nodules, but for patients with N2 and N3 nodules, RND is neccessary to eradicate the nodal metastases. Moreover, the postoperative radiotherapy is indispensable for ruling out the occult cervical lymph node metastaese in selective neck dissection.     

Prediction of cervical lymph node metastasis in squamous cell carcinoma of the tongue/floor of mouth

BACKGROUND: Cervical lymph node metastasis has a major influence on survival in oral cancer. However, the factors influencing its occurrence are uncertain. Our aim was to improve the prognostic efficiency of the histologic assessment of the primary tumor in predicting metastasis in an individual patient. METHODS: The relationship between selected clinical and histologic features of the primary tumor of tongue/floor of the mouth and the actual metastatic status was investigated in 45 patients. Invasive cell grading was supplemented by histologic measurements of tumor size and assessments of vascular and perineural invasion. RESULTS: Ten histologic features showed significant differences in relation to metastasis. A logistic regression model with two predictor variables (total histologic malignancy score and vascular invasion) classified correctly 39 (87%) of the 45 cases. CONCLUSIONS: Histologic assessment of tumor size and malignancy grade are useful in predicting metastasis. Vascular and perineural invasion are important predictors and should be included in multifactorial malignancy grading schemes. Application of the prognostic index to the biopsy specimen would aid in treatment planning.     

Current results of the treatment of cervical metastatic lymph nodes by concurrent hyperfractionation of carboplatin and irradiation

The results of the treatment of metastatic neck nodes is evaluated after a mean follow-up of 24 months (maximum 45 months). Fifty-seven patients with epidermoid carcinoma of the head and neck were treated according to a hyperfractionated chemoradiation schedule including two fractions a day. Each fraction consisted of 10 mg carboplatin + 115 cGy. Two fractions were given each day, five days a week, for a total dose of 700 mg carboplatin + 8050 cGy. Whenever possible, surgical salvage was performed if treated nodes persisted or recurred. Ten patients presented with N0, 8 with N1, 7 with N2a, 4 with N2b, 7 with N2c, and 21 with N3. The classification of the primary tumor was: 3 Tx, 6 T2, 9 T3 and 39 T4. One hundred and eleven nodes were treated (62 with a diameter of 1-3 cm, 26 with a diameter of 3-6 cm and 23 with a diameter over 6 cm). Actuarial node controls were: 100% for N0, 97% for nodes 1-3 cm, 87% for nodes 3-6 cm, 95% for nodes over 6 cm and 97% for the whole group. The actuarial local-regional control was 71% and the disease-free survival was 60%. These results include 5 surgical salvages (11% of N+), 2 of which recurred again (40%), while another 3 (60%) did not recur.     

Massive lower gastrointestinal haemorrhage secondary to metastatic squamous cell carcinoma of the lung

Clinically significant symptoms due to gastrointestinal metastases from primary lung cancers is rare. A case of life-threatening lower gastrointestinal haemorrhage secondary to metastatic squamous cell carcinoma of the lung is reported. Previous reports of such metastases are reviewed, with reference to management and prognosis. After resection of colonic metastases from squamous cell lung cancer, survival is similar to that for primary disease. It is suggested that patients with known or suspected squamous cell lung cancer presenting with lower gastrointestinal symptoms be managed as aggressively as those with no previous history of disease.     

Characterization of primary and metastatic cell lines established from a patient with renal cell carcinoma

Prolonged hypoxia induced transient drug resistance in Chinese hamster lung fibroblasts. Previously hypoxic cells were resistant to adriamycin and resistant to etoposide. Complete recovery of etoposide sensitivity was observed following reaeration for 24 hr. A change in P-glycoprotein expression was unlikely to contribute to the resistance caused by hypoxia, since adriamycin resistance was not reversed by verapamil. However, alteration in the plasma membrane structure may be involved, since previously hypoxic cells were resistant to extracellular superoxide radical generated by the addition of xanthine/xanthine oxidase. In contrast, adriamycin sensitivity was not altered by hypoxia in 3 human breast-cancer cell lines. MDA-468 and MCF-7/Adr differed in their response to EGF, independent of the presence of hypoxia. These results suggest that hypoxic-stress-induced drug resistance is not generalized.     

Myasthenia gravis and primary squamous cell carcinoma of the thymus

Occurrence of primary squamous cell carcinoma of the thymus gland in a 65-year-old man with myasthenia gravis is reported. Histologic and immunohistochemical studies confirmed the diagnosis of a differentiated squamous cell carcinoma. Extensive clinical investigations ruled out another primary site for the tumor. The patient made a full recovery postoperatively. Only three cases of primary squamous cell carcinoma of the thymus gland in association with myasthenia gravis have been reported in the literature.     

Multiple primary cancers in esophageal squamous cell carcinoma: incidence and implications

BACKGROUND: Uraemia and chronical haemodialysis are associated with an abnormal growth hormone (GH)-insulin-like growth factor (IGF) axis which may contribute to malnutrition and renal bone disease. Short-term studies have shown a beneficial effect of treatment with recombinant human growth hormone (rhGH) on nutritional status in patients on haemodialysis. In the present study, we evaluated the effect of rhGH on bone and mineral metabolism. METHODS: Twenty chronic malnourished patients on haemodialysis took part in a double-blind, placebo controlled trial with subcutaneous injections of rhGH (4 IU/m2/day) or placebo for 6 months. RESULTS: During rhGH treatment, serum IGF-1 increased 264 +/- 52% (mean +/- SEM) (P < 0.008). There were no significant changes in biochemical markers of mineral metabolism (serum ionized calcium, phosphate and parathyroid hormone). Among markers of bone metabolism, there was a significant increase in serum procollagen type I C-terminal propeptide (maximum 155 +/- 8%, P < 0.001) and no significant changes in serum alkaline phosphatase. Bone densitometry showed a significant decrease in whole body bone mineral content (95.7 +/- 1.2%) after 6 months treatment. The effects on the proximal femur were not significant. CONCLUSION: The effects of 6 months treatment with rhGH seen in this study are best explained by a GH- or IGF-1-induced increased bone turnover. Long-term treatment in larger cohorts followed by bone densitometry and, preferentially, bone histomorphometry are needed to evaluate whether this is a beneficial effect in haemodialysis patients.     

Mast cell activation and migration to lymph nodes during induction of an immune response in mice

The mast cell response in skin and lymph nodes was examined during the sensitization phase of dinitrofluorobenzene (DNFB)-induced contact hypersensitivity in mice. Degranulation of 62% of mast cells in DNFB-exposed skin was evident within 30 min of a dual application of DNFB, reaching a peak of 77% at 24 h, and persisting in 42% after 5 d. Abundant expression of macrophage inflammatory protein (MIP)-1alpha and MIP-1beta mRNAs and proteins was observed in keratinocytes, and mast cell degranulation was significantly inhibited after administration of neutralizing antibodies to MIP-1alpha, but not MIP-1beta. During DNFB sensitization, the mast cell density in the skin decreased by half, concurrent with a fivefold expansion of mast cell numbers in draining lymph nodes. Fluorescent-labeled mast cells injected into the skin appeared in draining lymph nodes after application of DNFB, followed by subsequent migration to the spleen. In lymph nodes, mast cells were an abundant and predominant source of MIP-1beta, neutralization of which partially inhibited T lymphocyte recruitment. These results indicate that mast cells contribute to the induction of this primary immune response by activation at and migration from the site of antigen encounter to draining lymph nodes, wherein they mediate T lymphocyte recruitment by production of MIP-1beta.     

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.     

Cervical carcinoma metastatic to para-aortic nodes: extended field radiation therapy with concomitant 5-fluorouracil and cisplatin chemotherapy: a Gynecologic Oncology Group study

PURPOSE: A multicenter trial of chemoradiation therapy to evaluate the feasibility of extended field radiation therapy (ERT) with 5-fluorouracil (5-FU) and cisplatin, and to determine the progression-free interval (PFI), overall survival (OS), and recurrence sites in patients with biopsy-confirmed para-aortic node metastases (PAN) from cervical carcinoma. METHODS AND MATERIALS: Ninety-five patients with cervical carcinoma and PAN metastases were entered and 86 were evaluable: Stage I--14, Stage II--40, Stage III--27, Stage IVA--5. Seventy-nine percent of the patients were followed for 5 or more years or died. ERT doses were 4500 cGy (PAN), 3960 cGy to the pelvis (Stages IB/IIB), and 4860 cGy to the pelvis (Stages IIIB/IVA). Point A intracavitary (IC) doses were 4000 cGy (Stages IB/IIB), and 3000 cGy (Stages IIIB/IVA). Point B doses were raised to 6000 cGy (ERT + IC) with parametrial boost. Concomitant chemotherapy consisted of 5-FU 1000 mg/m2/day for 96 hours and cisplatin 50 mg/m2 in weeks 1 and 5. RESULTS: Eighty-five of 86 patients completed radiation therapy and 90% of patients completed both courses of chemotherapy. Gynecologic Oncology Group (GOG) grade 3-4 acute toxicity were gastrointestinal (18.6%) and hematologic (15.1%). Late morbidity actuarial risk of 14% at 4 years primarily involved the rectum. Initial sites of recurrence were pelvis alone, 20.9%; distant metastases only, 31.4%; and pelvic plus distant metastases, 10.5%. The 3-year OS and PFI rate were 39% and 34%, respectively, for the entire group. OS was Stage I--50%, Stage II--39%, and Stage III/IVA--38%. CONCLUSIONS: Extended field radiation therapy with 5-FU and cisplatin chemotherapy was feasible in a multicenter clinical trial. PFI of 33% at 3 years suggests that a proportion of patients achieve control of advanced pelvic disease and that not all patients with PAN metastases have systemic disease. This points to the importance of assessment and treatment of PAN metastases.